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

2000 ◽  
Vol 9 (6) ◽  
pp. 1-6 ◽  
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.

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

2003 ◽  
Vol 99 (4) ◽  
pp. 738-745 ◽  
Author(s):  
Yoshitaka Yamada ◽  
Toshihiko Kuroiwa ◽  
Toshimasa Nakagawa ◽  
Yoshinaga Kajimoto ◽  
Takehiko Dohi ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Tumor Cell ◽  
Cell Lines ◽  
Splice Variants ◽  
Expression Patterns ◽  
Tumor Cell Lines ◽  
Content Type ◽  
Malignant Brain Tumors ◽  
Fine Print

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.

LOCAL HYPERTHERMIA IN TREATMENT FOR MALIGNANT BRAIN TUMORS

2018 ◽  
Vol 64 (1) ◽  
pp. 54-61
Author(s):  
A. Ryabova ◽  
O. Gribova ◽  
V. Novikov ◽  
E. Choinzonov ◽  
Zh. Starceva ◽  
...  
Keyword(s):  
Experimental Data ◽  
Radiation Therapy ◽  
Brain Tumors ◽  
Tumor Cells ◽  
Combined Treatment ◽  
Complex Treatment ◽  
Local Hyperthermia ◽  
Malignant Brain Tumors ◽  
Sensitizing Effect ◽  
Methods Of Treatment

Unsatisfactory results of complex treatment for malignant brain tumors stimulate search of new effective methods of treatment. Radiation therapy is an integral part of the combined treatment but often does not influence lethally on resistant tumor cells. Thereby in recent decades there has been an active search for different modifiers, which can increase the sensitivity of tumors to chemotherapy and radiotherapy. One of the universal sensitizers is the local hyperthermia. Experimental data showed that the effect of high temperatures had both a direct damaging effect on tumor cells and a sensitizing effect. The literature review given in the article provides an overview of the existing methods of the local hyperthermia for brain tumors treatment.

scholarly journals Silencing ZEB2 Induces Apoptosis and Reduces Viability in Glioblastoma Cell Lines

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 901
Author(s):  
Sahar Safaee ◽  
Masoumeh Fardi ◽  
Nima Hemmat ◽  
Neda Khosravi ◽  
Afshin Derakhshani ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Brain Tumor ◽  
Brain Tumors ◽  
Cell Lines ◽  
Scratch Test ◽  
Cycle Arrest ◽  
U373 Cell ◽  
Brain Tumor Cell ◽  
Induced Apoptosis ◽  
Glioma Tumors

Background: Glioma is an aggressive type of brain tumor that originated from neuroglia cells, accounts for about 80% of all malignant brain tumors. Glioma aggressiveness has been associated with extreme cell proliferation, invasion of malignant cells, and resistance to chemotherapies. Due to resistance to common therapies, glioma affected patients’ survival has not been remarkably improved. ZEB2 (SIP1) is a critical transcriptional regulator with various functions during embryonic development and wound healing that has abnormal expression in different malignancies, including brain tumors. ZEB2 overexpression in brain tumors is attributed to an unfavorable state of the malignancy. Therefore, we aimed to investigate some functions of ZEB2 in two different glioblastoma U87 and U373 cell lines. Methods: In this study, we investigated the effect of ZEB2 knocking down on the apoptosis, cell cycle, cytotoxicity, scratch test of the two malignant brain tumor cell lines U87 and U373. Besides, we investigated possible proteins and microRNA, SMAD2, SMAD5, and miR-214, which interact with ZEB2 via in situ analysis. Then we evaluated candidate gene expression after ZEB2-specific knocking down. Results: We found that ZEB2 suppression induced apoptosis in U87 and U373 cell lines. Besides, it had cytotoxic effects on both cell lines and reduced cell migration. Cell cycle analysis showed cell cycle arrest in G0/G1 and apoptosis induction in U87 and U373 cell lines receptively. Also, we have found that SAMAD2/5 expression was reduced after ZEB2-siRNA transfection and miR-214 upregulated after transfection. Conclusions: In line with previous investigations, our results indicated a critical oncogenic role for ZEB2 overexpression in brain glioma tumors. These properties make ZEB2 an essential molecule for further studies in the treatment of glioma cancer.

Multiagent Chemotherapy and Deferred Radiotherapy in Infants With Malignant Brain Tumors: A Report From the Children’s Cancer Group

2005 ◽  
Vol 23 (30) ◽  
pp. 7621-7631 ◽  
Author(s):  
J. Russell Geyer ◽  
Richard Sposto ◽  
Mark Jennings ◽  
James M. Boyett ◽  
Richard A. Axtell ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Brain Tumors ◽  
Induction Chemotherapy ◽  
Metastatic Disease ◽  
Response Rate ◽  
Residual Tumor ◽  
Study Entry ◽  
Receive Radiation Therapy ◽  
Malignant Brain Tumors ◽  
Significant Difference

Purpose To evaluate response rate, event-free survival (EFS), and toxicity of two chemotherapeutic regimens for treatment of children younger than 36 months with malignant brain tumors and to estimate control intervals without irradiation in children with no residual tumor after initial surgery and induction chemotherapy and with delayed irradiation in patients with residual tumor or metastatic disease at diagnosis. Patients and Methods Patients were randomly assigned to one of two regimens of induction chemotherapy (vincristine, cisplatin, cyclophosphamide, and etoposide v vincristine, carboplatin, ifosfamide, and etoposide). Maintenance chemotherapy began after induction in children without progressive disease. Children with no residual tumors after induction therapy and no metastatic disease at diagnosis were not to receive radiation therapy unless their tumors progressed. Results Two hundred ninety-nine infants were enrolled. Forty-two percent of patients responded to induction chemotherapy. At 5 years from study entry, the EFS rate was 27% ± 3%, and the survival rate was 43% ± 3%. There was no significant difference between the two arms in terms of response rate or EFS. For medulloblastoma, supratentorial primitive neuroectodermal tumor, ependymoma, and rhabdoid tumors, 5-year EFS rates were 32% ± 5%, 17% ± 6%, and 32% ± 6%, and 14% ± 7%, respectively. Fifty-eight percent of patients who were alive 5 years after study entry had not received radiation therapy. Conclusion Intensified induction chemotherapy resulted in a high response rate of malignant brain tumors in infants. Survival was comparable to that of previous studies, and most patients who survived did not receive radiation therapy.

Radiation therapy for malignant brain tumors in infants less than 36 months old: Compliance and survival

2000 ◽  
Vol 48 (3) ◽  
pp. 180 ◽  
Author(s):  
M.L Tao ◽  
J.A Turner ◽  
J.R Geyer ◽  
B Donahue ◽  
R Sposto ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Brain Tumors ◽  
Malignant Brain Tumors

scholarly journals Effect of Lymphokine—activated Killer Cells with or without Radiation Therapy against Malignant Brain Tumors

1995 ◽  
Vol 35 (1) ◽  
pp. 22-27 ◽  
Author(s):  
Kunio NAKAGAWA ◽  
Takao KAMEZAKI ◽  
Yasushi SHIBATA ◽  
Takashi TSUNODA ◽  
Kotoo MEGURO ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Brain Tumors ◽  
Lymphokine Activated Killer Cells ◽  
Killer Cells ◽  
Malignant Brain Tumors

Maternal embryonic leucine zipper kinase is a key regulator of the proliferation of malignant brain tumors, including brain tumor stem cells

2008 ◽  
Vol 86 (1) ◽  
pp. 48-60 ◽  
Author(s):  
Ichiro Nakano ◽  
Michael Masterman-Smith ◽  
Kuniyasu Saigusa ◽  
Andres A. Paucar ◽  
Steve Horvath ◽  
...  
Keyword(s):  
Stem Cells ◽  
Brain Tumor ◽  
Brain Tumors ◽  
Leucine Zipper ◽  
Tumor Stem Cells ◽  
Malignant Brain Tumors ◽  
Brain Tumor Stem Cells
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