miRNA-26a expression influences the therapy response to carmustine wafer implantation in patients with glioblastoma multiforme

Abstract Background Glioblastoma multiforme (GBM) represents nearly 50% of all malignant brain tumours. Molecular and genomic diagnostics are beginning to unravel the variation between individual tumours. However, there is growing evidence that cellular heterogeneity exists within a single malignancy. Singe cell analysis has demonstrated the presence of subpopulations corresponding to distinct expression profiles. Objective and experimental approach characterisation of the intratumor heterogeneity is essential to understand biological behaviour and therapy response. Through combining a genetically labelled mouse model (rosa26-confetti lineage tracing locus) with genetically engineered GBM model we can label distinct cellular lineages. Results For three-dimensional imaging of these fluorescently labelled tumours we have optimised tissue clearing protocols. Fluorescence activated sorting of genetically labelled tumour cells identifies distinct populations within single tumours. With these techniques can now interrogate the spatial organisation of clones across large areas and we can compare distinct tumour lineages. Outlook Currently, we are engineering human glioblastoma cell lines with genetic fluorescent labels for lineage tracing. Several genetically characterised human cell lines are available for which novel therapeutic targets have been identified. We will apply our lineage tracing approach to investigate the clonal effects of these tailored therapeutics.

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Comparison of early versus late onset of cellular immunotherapy in glioblastoma multiforme WHO IV.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e13531 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e13531-e13531

Author(s):

Jan Nesselhut ◽

Dagmar Marx ◽

Nicole Cillien ◽

Raymond Y. Chang ◽

Wulf-Peter Brockmann ◽

...

Keyword(s):

Overall Survival ◽

Survival Rate ◽

Dendritic Cell ◽

Glioblastoma Multiforme ◽

Therapy Response ◽

Newly Diagnosed ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Stupp Protocol

e13531 Background: Glioblastoma multiforme (GBM WHO grade IV glioma) is an aggressive disease with an unfavorable prognosis. The current first line treatment comprises radical operation and radiotherapy combined with temozolomide chemotherapy (Stupp protocol). After failure of first-line therapy there is currently no effective therapy. Here we report that dendritic cell therapy prolongs the survival for patients with newly diagnosed GBM V. Preliminary results show that adding checkpoint blockade with Nivolumab may cause a secondary therapy response. Methods: After isolating monocytes from peripheral blood of n = 11 patients with stage IV GBM, who underwent primary surgery and first-line radio-chemotherapy and from n = 34 patients, who failed first line therapy MoDC were generated using standard protocols. In 5 patients checkpoint blockade with Nivolumab was added after failure of DC therapy. Results: With a median overall survival of 41 months there is a clear improvement of the overall survival in patients, who received DC therapy after having finished the Stupp-protocol. The 3- year-survival rate after primary diagnosis is 46% (n = 5) and 1 patient is still alive after 81 months. In this patient a secondary therapy response of 16 months could be induced by adding low dose Nivolumab (1mg/kg body weight) after failure of DC therapy. The median survival after onset of DC therapy in patients who failed first line standard therapy is 10 months. The 3-year overall survival rate is 9% (n = 3). In 4 patients therapy with Nivolumab was combined causing only a limiting effect on the survival (4 to 10 months). Conclusions: Dendritic-cell based immune therapy started immediately after primary standard therapy has a clear impact on the overall survival of patients with newly diagnosed GBM IV. Whereas the therapeutic effect for patients after failure of first-line therapy is limited. Nivolumab may cause secondary therapy response in certain patients.

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Prognostic impact of O6-methylguanine-DNA methyltransferase silencing in patients with recurrent glioblastoma multiforme who undergo surgery and carmustine wafer implantation

Cancer ◽

10.1002/cncr.24546 ◽

2009 ◽

Vol 115 (20) ◽

pp. 4783-4794 ◽

Cited By ~ 61

Author(s):

Philippe Metellus ◽

Bema Coulibaly ◽

Isabelle Nanni ◽

Frederic Fina ◽

Nathalie Eudes ◽

...

Keyword(s):

Glioblastoma Multiforme ◽

Dna Methyltransferase ◽

Recurrent Glioblastoma ◽

Prognostic Impact ◽

Recurrent Glioblastoma Multiforme ◽

Methylguanine Dna Methyltransferase ◽

Carmustine Wafer

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DIFFERENCES OF TEMOZOLAMIDE RESPONSE IN GLIOBLASTOMA MULTIFORME: REPORT OF TWO CASES

Callosum Neurology ◽

10.29342/cnj.v3i3.89 ◽

2020 ◽

Vol 3 (3) ◽

pp. 118-126

Author(s):

Djohan Ardiansyah ◽

Vita Kusuma Rahmawati ◽

Sri Andreani Utomo

Keyword(s):

Prognostic Factors ◽

Glioblastoma Multiforme ◽

Clinical Manifestations ◽

Brain Magnetic Resonance Imaging ◽

Therapy Response ◽

Response Assessment ◽

Complete Response ◽

Adult Brain ◽

Rano Criteria ◽

Standard Management

Background: Glioblastoma multiforme (GBM) is about 20% of primary adult brain neoplasms which has poor prognosis; life expectancy is no more than 12 months after the diagnosis. Temozolomide (TMZ) has become GBM standard therapy, combined with the surgery and radio-chemotherapy. Evaluation is important since its relation with the continuity or termination of therapy. Several studies are improving to measure therapy response of GBM. Response Assessment in Neuro-Oncology (RANO) criteria which is published in 2010, became a major criterias to evaluate TMZ response in patients with GBM. This criteria combines clinical manifestation, steroid therapy, and brain magnetic resonance imaging (MRI). Case: We report two GBM cases with standard management. Two women in productive ages and specific clinical manifestations, diagnosed with GBM in left temporal lobes. A 24-year-old woman showed complete response; while a-41-year old one showed progressive response. Discussion: We analyze TMZ response based on RANO criteria. Prognostic factors that differentiate TMZ response in both cases were presence of comorbidity, intratumoral hemorrhage on MRI, and surgery initiation in early diagnosis. Conclusion: Based on RANO criteria and prognostic factors which support TMZ response, the role of adjuvant TMZ become important in standard management of GBM. Keywords: Glioblastoma Multiforme, Response Assessment in Neuro-Oncology, Temozolomide.

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