scholarly journals Toxin-Based Targeted Therapy for Malignant Brain Tumors

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Vidyalakshmi Chandramohan ◽  
John H. Sampson ◽  
Ira Pastan ◽  
Darell D. Bigner
Keyword(s):  
Brain Tumors ◽  
Cytotoxic Agents ◽  
Treatment Modalities ◽  
Drug Candidates ◽  
Protein Conjugates ◽  
Malignant Brain Tumors ◽  
Disease Stabilization ◽  
Survival Prolongation ◽  
Specific Antigens ◽  
Cytotoxic Proteins

Despite advances in conventional treatment modalities for malignant brain tumors—surgery, radiotherapy, and chemotherapy—the prognosis for patients with high-grade astrocytic tumor remains dismal. The highly heterogeneous and diffuse nature of astrocytic tumors calls for the development of novel therapies. Advances in genomic and proteomic research indicate that treatment of brain tumor patients can be increasingly personalized according to the characteristics of the targeted tumor and its environment. Consequently, during the last two decades, a novel class of investigative drug candidates for the treatment of central nervous system neoplasia has emerged: recombinant fusion protein conjugates armed with cytotoxic agents targeting tumor-specific antigens. The clinical applicability of the tumor-antigen-directed cytotoxic proteins as a safe and viable therapy for brain tumors is being investigated. Thus far, results from ongoing clinical trials are encouraging, as disease stabilization and patient survival prolongation have been observed in at least 109 cases. This paper summarizes the major findings pertaining to treatment with the different antiglioma cytotoxins at the preclinical and clinical stages.

Cytostatic Agents in the Management of Malignant Gliomas

1998 ◽  
Vol 5 (2) ◽  
pp. 150-162 ◽  
Author(s):  
Tom Mikkelsen
Keyword(s):  
Signal Transduction ◽  
Brain Tumors ◽  
Tumor Invasion ◽  
Proteinase Inhibitors ◽  
Malignant Gliomas ◽  
Cytotoxic Agents ◽  
Management Approach ◽  
Cytostatic Agents ◽  
Management Options ◽  
Malignant Brain Tumors

Background: Cytotoxic therapy for malignant gliomas is limited by poor delivery and drug resistance, and local therapy is ineffective in managing migratory cells. However, recent developments in malignant glioma therapy involve trials of cytostatic rather than conventional cytotoxic agents. Methods: The biology of the brain extracellular matrix, tumor invasion, and angiogenesis are reviewed, and the cytostatic agents that inhibit matrix metalloproteinases, angiogenesis, cell proliferation, and signal transduction are discussed, as well as studies of the angiogenic and migratory capacity of malignant brain tumors. Results: Two specific and interrelated areas, anti-invasion (migration) and anti-angiogenesis, are potential areas to develop new treatment strategies. Tumor invasion and angiogenesis are important components of the spread and biologic effects of malignant gliomas. Several proteinase inhibitors are in clinical trial, as well as anti-angiogenic agents and signal transduction cascade inhibitors. Conclusions: Biologic control of brain tumor cell populations may offer a new management approach to add to currently available management options for malignant brain tumors.

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.

scholarly journals Radiotherapy, Especially at Young Age, Increases the Risk for De Novo Brain Tumors in Patients Treated for Pituitary/Sellar Lesions

2017 ◽  
Vol 102 (3) ◽  
pp. 1051-1058 ◽  
Author(s):  
Pia Burman ◽  
André P. van Beek ◽  
Beverly M. K. Biller ◽  
Cecilia Camacho-Hübner ◽  
Anders F. Mattsson
Keyword(s):  
Brain Tumors ◽  
De Novo ◽  
Pituitary Tumors ◽  
Incidence Rates ◽  
Treatment Modalities ◽  
Regression Methods ◽  
Malignant Brain Tumors ◽  
Sellar Lesions ◽  
Increased Risk ◽  
Rate Ratios

Abstract Context: De novo brain tumors developing after treatment of pituitary/sellar lesions have been reported, but it is unknown whether this is linked to any of the treatment modalities. Objective: To study the occurrence of malignant brain tumors and meningiomas in a large cohort of patients treated for pituitary/sellar lesions, with special emphasis on the role of radiotherapy (RT). Patients and Methods: Patients (n = 8917) who were hypopituitary due to pituitary adenomas, craniopharyngiomas, and other sellar tumors followed in KIMS (Pfizer International Metabolic Database) from 1994 to 2012 were included. Treatment consisted of surgery and/or medical therapy in 4927 patients, RT alone, or with surgery in 3236 patients; data were missing in 754. Incidence rate ratios (RRs) were analyzed through Poisson regression methods with internal comparisons. Results: During 53,786 patient-years, 17 cases of malignant brain tumors (13 exposed to RT) and 27 meningiomas (22 exposed to RT) were reported. RR for RT vs no RT was 3.34 [95% confidence interval (CI), 1.06 to 10.6] for malignant brain tumors, and 4.06 (95% CI, 1.51 to 10.9) for meningiomas. The risk of developing a malignant brain tumor increased by 2.4-fold (P = 0.005) and meningioma by 1.6-fold with every 10 years of younger age at RT (P = 0.05). Incidence rates were similar in patients treated with conventional RT compared with stereotactic RT. Conclusion: RT of pituitary tumors is associated with increased risk of developing malignant brain tumors and meningiomas, especially when given at younger ages. In balancing risks and benefits of RT, our findings emphasize that special consideration should be given to the age of the patient.

Identification of new scaffolds with anti-tumor action toward human glioblastoma cells

MedChemComm ◽  
2016 ◽  
Vol 7 (12) ◽  
pp. 2428-2434 ◽  
Author(s):  
Aleksandra Ellert-Miklaszewska ◽  
Sabrina Dallavalle ◽  
Loana Musso ◽  
Nadine Martinet ◽  
Kamil Wojnicki ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Hdac Inhibitors ◽  
Glioblastoma Cells ◽  
Human Glioblastoma ◽  
Drug Candidates ◽  
Malignant Brain Tumors ◽  
Human Glioblastoma Cells

Compounds containing an isothiazolonaphthoquinone core and HDAC inhibitors with an indolyl-substituted biphenyl-4-yl-acrylohydroxamic acid are promising drug candidates against malignant brain tumors, glioblastomas.

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 The Challenge of Diagnosing Constitutional Mismatch Repair Deficiency Syndrome in Brain Malignancies from Young Individuals

2021 ◽  
Vol 22 (9) ◽  
pp. 4629
Author(s):  
Cristina Carrato ◽  
Carolina Sanz ◽  
Ana María Muñoz-Mármol ◽  
Ignacio Blanco ◽  
Marta Pineda ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Mismatch Repair ◽  
Rare Event ◽  
Deficiency Syndrome ◽  
Mismatch Repair Deficiency ◽  
Malignant Brain Tumors ◽  
Repair Deficiency ◽  
Clinical Awareness ◽  
High Degree ◽  
Constitutional Mismatch Repair Deficiency

Biallelic germline mismatch repair (MMR) gene (MLH1, MSH2, MSH6, and PMS2) mutations are an extremely rare event that causes constitutional mismatch repair deficiency (CMMRD) syndrome. CMMRD is underdiagnosed and often debuts with pediatric malignant brain tumors. A high degree of clinical awareness of the CMMRD phenotype is needed to identify new cases. Immunohistochemical (IHC) assessment of MMR protein expression and analysis of microsatellite instability (MSI) are the first tools with which to initiate the study of this syndrome in solid malignancies. MMR IHC shows a hallmark pattern with absence of staining in both neoplastic and non-neoplastic cells for the biallelic mutated gene. However, MSI often fails in brain malignancies. The aim of this report is to draw attention to the peculiar IHC profile that characterizes CMMRD syndrome and to review the difficulties in reaching an accurate diagnosis by describing the case of two siblings with biallelic MSH6 germline mutations and brain tumors. Given the difficulties involved in early diagnosis of CMMRD we propose the use of the IHC of MMR proteins in all malignant brain tumors diagnosed in individuals younger than 25 years-old to facilitate the diagnosis of CMMRD and to select those neoplasms that will benefit from immunotherapy treatment.

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