Transcriptional expression of survivin and its splice variants in brain tumors in humans

Object. Survivin, one of the apoptosis inhibitor proteins, has been detected in most cancers in humans. In addition, two splice variants (survivin-2B and survivin-ΔEx3) have been identified. The authors investigated the transcription levels of survivin messenger (m)RNA and its splice variants in nine tumor cell lines, including gliomas, and in 25 brain tumor samples, by performing quantitative reverse transcription-polymerase chain reaction. The correlation between transcript expression levels and pathological findings were also analyzed. Methods. Transcription levels were measured using primer pairs specific for survivin and either of its splice variants and were normalized to the glyceraldehyde 6-phosphate dehydrogenase. Among the tumor cell lines tested, glioblastoma cell lines showed the highest levels of survivin expression. Among brain tumor samples studied, survivin was preferentially expressed in malignant brain tumors and gliomas. The relative expression level of survivin-ΔEx3/survivin was significantly higher in malignant than in benign brain tumor samples. Expression patterns were dominant for survivin-ΔEx3 in malignant brain tumors and dominant for survivin-2B in benign ones. A significant linear correlation between survivin mRNA expression and MIB-1 labeling index was demonstrated in all brain tumor samples. Conclusions. The authors' results indicate that quantifying the levels of survivin and its splice variants is useful for the prediction of the cell biological malignancy of gliomas, independent of their pathological features.

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Thiamine-deficient lactic acidosis with brain tumor treatment

Journal of Neurosurgery ◽

10.3171/jns.1998.89.6.1025 ◽

1998 ◽

Vol 89 (6) ◽

pp. 1025-1028 ◽

Cited By ~ 4

Author(s):

Hiroshi Kuba ◽

Takanori Inamura ◽

Kiyonobu Ikezaki ◽

Masatou Kawashima ◽

Masashi Fukui

Keyword(s):

Brain Tumor ◽

Lactic Acidosis ◽

Brain Tumors ◽

Neurological Deficits ◽

High Dose ◽

Content Type ◽

Malignant Brain Tumors ◽

Level Of Consciousness ◽

Lactic Acidemia ◽

Fine Print

✓ Lactic acidosis due to thiamine deficiency is known to complicate chemotherapy and radiotherapy treatment of malignant extracranial tumors, but to the authors' knowledge, this complication has not been reported in patients treated for malignant brain tumors. They report three such cases, demonstrating that this complication can occur during treatment of brain tumors. In all patients, consciousness levels deteriorated within 1 to 2 days. Serum lactic acid levels increased to concentrations between 62 and 96.7 mg/dl, resulting in severe metabolic acidosis. A low blood thiamine level (9 ng/ml) was demonstrated at the onset in one case, and high-dose thiamine infusions dramatically improved lactic acidemia as well as impairment of consciousness in two cases. In the other case, hydrocephalus was suspected initially, resulting in a delay in thiamine supplementation. Clinical differentiation of this form of lactic acidosis from hydrocephalus or tumor progression can be very difficult in a patient undergoing treatment for a malignant brain tumor. Demand for thiamine is thought to be increased in patients with malignant brain tumors, and supplemental thiamine during treatment is necessary to prevent lactic acidosis. When this complication occurs, immediate treatment with sufficient thiamine is essential, together with normalization of pH by using sodium bicarbonate. With timely intervention, the level of consciousness can recover to the preacidotic state with no new neurological deficits.

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Real-Time RT-PCR Quantification of Human Telomerase Reverse Transcriptase Splice Variants in Tumor Cell Lines and Non–Small Cell Lung Cancer

Clinical Chemistry ◽

10.1373/clinchem.2006.073015 ◽

2007 ◽

Vol 53 (1) ◽

pp. 53-61 ◽

Cited By ~ 29

Author(s):

Eleni Mavrogiannou ◽

Areti Strati ◽

Aliki Stathopoulou ◽

Emily G Tsaroucha ◽

Loukas Kaklamanis ◽

...

Keyword(s):

Tumor Cell ◽

Real Time ◽

Cell Lines ◽

Splice Variant ◽

Splice Variants ◽

Telomerase Activity ◽

Tumor Cell Lines ◽

Rt Pcr ◽

Human Telomerase Reverse Transcriptase ◽

Tissue Samples

Abstract Background: We developed and validated a real-time reverse transcription (RT)–PCR for the quantification of 4 individual human telomerase reverse transcriptase (TERT) splice variants (α+β+, α−β+, α+β−, α−β−) in tumor cell lines and non–small cell lung cancer (NSCLC). Methods: We used in silico designed primers and a common TaqMan probe for highly specific amplification of each TERT splice variant, PCR transcript–specific DNA external standards as calibrators, and the MCF-7 cell line for the development and validation of the method. We then quantified TERT splice variants in 6 tumor cell lines and telomerase activity and TERT splice variant expression in cancerous and paired noncancerous tissue samples from 28 NSCLC patients. Results: In most tumor cell lines, we observed little variation in the proportion of TERT splice variants. The α+β− splice variant showed the highest expression and α−β+ and α−β− the lowest. Quantification of the 4 TERT splice variants in NSCLC and surrounding nonneoplastic tissues showed the highest expression percentage for the α+β− variant in both NSCLC and adjacent nonneoplastic tissue samples, followed by α+β+, with the α−β+ and α−β− splice variants having the lowest expression. In the NSCLC tumors, the α+β+ variant had higher expression than other splice variants, and its expression correlated with telomerase activity, overall survival, and disease-free survival. Conclusions: Real-time RT-PCR quantification is a specific, sensitive, and rapid method that can elucidate the biological role of TERT splice variants in tumor development and progression. Our results suggest that the expression of the TERT α+β+ splice variant may be an independent negative prognostic factor for NSCLC patients.

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Variability in Gene Expression Patterns of Ewing Tumor Cell Lines Differing in EWS-FLI1 Fusion Type

Laboratory Investigation ◽

10.1038/labinvest.3780194 ◽

2000 ◽

Vol 80 (12) ◽

pp. 1833-1844 ◽

Cited By ~ 26

Author(s):

Dave N T Aryee ◽

Wolfgang Sommergruber ◽

Karin Muehlbacher ◽

Barbara Dockhorn-Dworniczak ◽

Andreas Zoubek ◽

...

Keyword(s):

Gene Expression ◽

Tumor Cell ◽

Cell Lines ◽

Expression Patterns ◽

Gene Expression Patterns ◽

Tumor Cell Lines ◽

Fusion Type ◽

Ewing Tumor

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Abstract 4334: Expression of PID1 correlates with PFS in pediatric medulloblastomas and negatively impacts growth of medulloblastoma, glioblastoma and AT/RT brain tumor cell lines

10.1158/1538-7445.am2012-4334 ◽

2012 ◽

Author(s):

Anat Erdreich-Epstein ◽

Xiuhai Ren ◽

Hong Zhou ◽

Matthew Schur ◽

Lingyun Ji ◽

...

Keyword(s):

Brain Tumor ◽

Tumor Cell ◽

Cell Lines ◽

Tumor Cell Lines ◽

Brain Tumor Cell

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Abstract 4176: Involvement of the lysosome in the cytotoxicity of Gallium Maltolate in human pediatric brain tumor cell lines

10.1158/1538-7445.am2020-4176 ◽

2020 ◽

Author(s):

Salvatore Molino ◽

Christopher R. Chitambar

Keyword(s):

Brain Tumor ◽

Tumor Cell ◽

Cell Lines ◽

Pediatric Brain Tumor ◽

Tumor Cell Lines ◽

Brain Tumor Cell ◽

Pediatric Brain

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Synthesis and in vitro cytotoxic activity of novel hexahydro-2H-pyrido[1,2-b]isoquinolines against human brain tumor cell lines

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/s0960-894x(97)10114-7 ◽

1997 ◽

Vol 7 (23) ◽

pp. 2945-2950 ◽

Cited By ~ 6

Author(s):

Axel Monsees ◽

Sabine Laschat ◽

Marc Hotfilder ◽

Johannes Wolff ◽

Klaus Bergander ◽

...

Keyword(s):

Brain Tumor ◽

Tumor Cell ◽

Human Brain ◽

Cytotoxic Activity ◽

Cell Lines ◽

Tumor Cell Lines ◽

Human Brain Tumor ◽

Brain Tumor Cell

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Pediatric Brain Tumor Cell Lines

Journal of Cellular Biochemistry ◽

10.1002/jcb.24976 ◽

2014 ◽

Vol 116 (2) ◽

pp. 218-224 ◽

Cited By ~ 33

Author(s):

Jingying Xu ◽

Ashley Margol ◽

Shahab Asgharzadeh ◽

Anat Erdreich-Epstein

Keyword(s):

Brain Tumor ◽

Tumor Cell ◽

Cell Lines ◽

Pediatric Brain Tumor ◽

Tumor Cell Lines ◽

Brain Tumor Cell ◽

Pediatric Brain

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WEE1 gene silencing can reduce Bcl2 expression in brain tumor cell lines

Clinical Biochemistry ◽

10.1016/j.clinbiochem.2011.08.506 ◽

2011 ◽

Vol 44 (13) ◽

pp. S205

Author(s):

Hosseini Ahmad ◽

Rahnama Susan ◽

Jaberipour Mansooreh ◽

Habib-Agahi Mojtaba

Keyword(s):

Brain Tumor ◽

Tumor Cell ◽

Gene Silencing ◽

Cell Lines ◽

Tumor Cell Lines ◽

Brain Tumor Cell ◽

Bcl2 Expression

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In vitro efficacy of recombinant diphtheria toxin–murine interleukin-4 immunoconjugate on mouse glioblastoma and neuroblastoma cell lines and the additive effect of radiation

Neurosurgical FOCUS ◽

10.3171/foc.2000.9.6.6 ◽

2000 ◽

Vol 9 (6) ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

Ki-Uk Kim ◽

Daniel A. Vallera ◽

Hsaio-Tzu Ni ◽

Kwan H. Cho ◽

Walter C. Low ◽

...

Keyword(s):

Radiation Therapy ◽

Brain Tumor ◽

Brain Tumors ◽

Cell Lines ◽

Diphtheria Toxin ◽

Cytotoxic Effect ◽

Neuroblastoma Cell ◽

Interleukin 4 ◽

Treatment Modalities ◽

Malignant Brain Tumors

Object The prognosis for patients with primary malignant brain tumors is poor despite aggressive treatment, and tumor recurrence is common regardless of the chosen therapy. Although multimodal treatment does not provide a cure, it is necessary to determine which treatment modalities have the greatest cytotoxic effect and can potentially prolong survival. Immunotoxin therapy is a novel approach for the treatment of tumors, and it has been successfully used in the central nervous system. Because the interleukin (IL)–4 receptor is commonly expressed on brain tumor cells, the purpose of this study was to evaluate the cytotoxic effect of using a modified diphtheria toxin–murine IL-4 (DT390-mIL4) immunoconjugate for the treatment of murine brain tumor cell lines and to determine whether the addition of radiation therapy could potentiate the effect of this agent. Methods Spontaneous murine glioblastoma (SMA-560) and two neuroblastoma (Neuro-2a and NB41A3) cell lines were treated using DT390-mIL4 at different concentrations, and the anti–mouse IL-4 monoclonal antibody (11B11) was used for blocking its cytotoxicity. Other SMA-560 and Neuro-2a cell lines were treated using 500 cGy of radiation 3 hours before DT390-mIL4 treatment. Cytotoxity was evaluated using a trypan blue viability assay. The immunoconjugate exhibited a dose-dependent cytotoxic effect with 50% inhibitory concentration values of 0.56 × 10−9 M in SMA-560, 1.28 × 10−9 M in Neuro-2a, and 0.95 × 10−10 M in NB41A3 cell lines. The cytotoxicity of DT390-mIL4 was specifically blocked by an excess of 11B11. Cytotoxicity was additive when the DT390-mIL4 at 10−9 M immunoconjugate administration was followed by radiation therapy. Conclusions These results indicate that the IL-4 receptor can be a target for diphtheria toxin fusion proteins and that radiation can potentiate the effects of DT390-mIL4. The development of multimodal approaches to treat malignant brain tumors with agents that have different mechanisms of action may be beneficial.

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