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Cancers
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Novel Techniques and Technology for Treatment of Brain Tumors
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Novel Techniques and Technology for Treatment of Brain Tumors

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Methods and Technologies Development".

Deadline for manuscript submissions: closed (20 October 2022) | Viewed by 15093

Special Issue Editor

Prof. Dr. David S. Baskin

E-Mail Website
Guest Editor
Department of Neurosurgery, Houston Methodist Hospital, Houston, TX 77030, USA
Interests: stroke; neurological surgery; brain tumors

Special Issue Information

Dear Colleagues,

Advances in molecular biology, virtual reality, optical imaging, and intraoperative techniques have revolutionized the treatment of brain tumors. This Special Issue will describe a number of these technologies, including selective mitochondrial chemotherapy for glioblastoma and the oncomagnetic treatment of cancer with high-frequency alternating magnetic fields. The use of oncolytic viruses and gene-mediated cytotoxic immunotherapy for brain-tumor treatment will be discussed, including the use of polio virus and various adenoviruses. The status of stem-cell therapy for brain tumors will be presented. Operative advances including awake craniotomy with brain mapping, the use of three-dimensional virtual reality, nuances in endoscopic skull base surgery, and robotic neurosurgical techniques will be described.

Prof. Dr. David S. Baskin
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • brain tumor
  • glioblastoma
  • immunotherapy
  • surgery

Published Papers (6 papers)

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Research

15 pages, 928 KiB  
Article
Prognostic Model for Intracranial Progression after Stereotactic Radiosurgery: A Multicenter Validation Study
by David J. Carpenter, Brahma Natarajan, Muzamil Arshad, Divya Natesan, Olivia Schultz, Michael J. Moravan, Charlotte Read, Kyle J. Lafata, Will Giles, Peter Fecci, Trey C. Mullikin, Zachary J. Reitman, John P. Kirkpatrick, Scott R. Floyd, Steven J. Chmura, Julian C. Hong and Joseph K. Salama
Cancers 2022, 14(21), 5186; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14215186 - 22 Oct 2022
Viewed by 1169
Abstract
Stereotactic radiosurgery (SRS) is a standard of care for many patients with brain metastases. To optimize post-SRS surveillance, this study aimed to validate a previously published nomogram predicting post-SRS intracranial progression (IP). We identified consecutive patients completing an initial course of SRS across [...] Read more.
Stereotactic radiosurgery (SRS) is a standard of care for many patients with brain metastases. To optimize post-SRS surveillance, this study aimed to validate a previously published nomogram predicting post-SRS intracranial progression (IP). We identified consecutive patients completing an initial course of SRS across two institutions between July 2017 and December 2020. Patients were classified as low- or high-risk for post-SRS IP per a previously published nomogram. Overall survival (OS) and freedom from IP (FFIP) were assessed via the Kaplan–Meier method. Assessment of parameters impacting FFIP was performed with univariable and multivariable Cox proportional hazard models. Among 890 patients, median follow-up was 9.8 months (95% CI 9.1–11.2 months). In total, 47% had NSCLC primary tumors, and 47% had oligometastatic disease (defined as ≤5 metastastic foci) at the time of SRS. Per the IP nomogram, 53% of patients were deemed high-risk. For low- and high-risk patients, median FFIP was 13.9 months (95% CI 11.1–17.1 months) and 7.6 months (95% CI 6.4–9.3 months), respectively, and FFIP was superior in low-risk patients (p < 0.0001). This large multisite BM cohort supports the use of an IP nomogram as a quick and simple means of stratifying patients into low- and high-risk groups for post-SRS IP. Full article
(This article belongs to the Special Issue Novel Techniques and Technology for Treatment of Brain Tumors)
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18 pages, 2880 KiB  
Article
Spermidine/Spermine N1-Acetyltransferase 1 (SAT1)—A Potential Gene Target for Selective Sensitization of Glioblastoma Cells Using an Ionizable Lipid Nanoparticle to Deliver siRNA
by Vinith Yathindranath, Nura Safa, Babu V. Sajesh, Kelly Schwinghamer, Magimairajan Issai Vanan, Rashid Bux, Daniel S. Sitar, Marshall Pitz, Teruna J. Siahaan and Donald W. Miller
Cancers 2022, 14(21), 5179; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14215179 - 22 Oct 2022
Cited by 5 | Viewed by 2936
Abstract
Spermidine/spermine N1-acetyltransferase 1 (SAT1) responsible for cell polyamine catabolism is overexpressed in glioblastoma multiforme (GB). Its role in tumor survival and promoting resistance towards radiation therapy has made it an interesting target for therapy. In this study, we prepared a lipid [...] Read more.
Spermidine/spermine N1-acetyltransferase 1 (SAT1) responsible for cell polyamine catabolism is overexpressed in glioblastoma multiforme (GB). Its role in tumor survival and promoting resistance towards radiation therapy has made it an interesting target for therapy. In this study, we prepared a lipid nanoparticle-based siRNA delivery system (LNP-siSAT1) to selectively knockdown (KD) SAT1 enzyme in a human glioblastoma cell line. The LNP-siSAT1 containing ionizable DODAP lipid was prepared following a microfluidics mixing method and the resulting nanoparticles had a hydrodynamic size of around 80 nm and a neutral surface charge. The LNP-siSAT1 effectively knocked down the SAT1 expression in U251, LN229, and 42MGBA GB cells, and other brain-relevant endothelial (hCMEC/D3), astrocyte (HA) and macrophage (ANA-1) cells at the mRNA and protein levels. SAT1 KD in U251 cells resulted in a 40% loss in cell viability. Furthermore, SAT1 KD in U251, LN229 and 42MGBA cells sensitized them towards radiation and chemotherapy treatments. In contrast, despite similar SAT1 KD in other brain-relevant cells no significant effect on cytotoxic response, either alone or in combination, was observed. A major roadblock for brain therapeutics is their ability to cross the highly restrictive blood–brain barrier (BBB) presented by the brain microcapillary endothelial cells. Here, we used the BBB circumventing approach to enhance the delivery of LNP-siSAT1 across a BBB cell culture model. A cadherin binding peptide (ADTC5) was used to transiently open the BBB tight junctions to promote paracellular diffusion of LNP-siSAT1. These results suggest LNP-siSAT1 may provide a safe and effective method for reducing SAT1 and sensitizing GB cells to radiation and chemotherapeutic agents. Full article
(This article belongs to the Special Issue Novel Techniques and Technology for Treatment of Brain Tumors)
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11 pages, 1453 KiB  
Article
Predicting Glioblastoma Cellular Motility from In Vivo MRI with a Radiomics Based Regression Model
by Kellen Mulford, Mariah McMahon, Andrew M. Gardeck, Matthew A. Hunt, Clark C. Chen, David J. Odde and Christopher Wilke
Cancers 2022, 14(3), 578; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14030578 - 24 Jan 2022
Cited by 2 | Viewed by 2469
Abstract
Characterizing the motile properties of glioblastoma tumor cells could provide a useful way to predict the spread of tumors and to tailor the therapeutic approach. Radiomics has emerged as a diagnostic tool in the classification of tumor grade, stage, and prognosis. The purpose [...] Read more.
Characterizing the motile properties of glioblastoma tumor cells could provide a useful way to predict the spread of tumors and to tailor the therapeutic approach. Radiomics has emerged as a diagnostic tool in the classification of tumor grade, stage, and prognosis. The purpose of this work is to examine the potential of radiomics to predict the motility of glioblastoma cells. Tissue specimens were obtained from 31 patients undergoing surgical resection of glioblastoma. Mean tumor cell motility was calculated from time-lapse videos of specimen cells. Manual segmentation was used to define the border of the enhancing tumor T1-weighted MR images, and 107 radiomics features were extracted from the normalized image volumes. Model parameter coefficients were estimated using the adaptive lasso technique validated with leave-one-out cross validation (LOOCV) and permutation tests. The R-squared value for the predictive model was 0.60 with p-values for each individual parameter estimate less than 0.0001. Permutation test models trained with scrambled motility failed to produce a model that out-performed the model trained on the true data. The results of this work suggest that it is possible for a quantitative MRI feature-based regression model to non-invasively predict the cellular motility of glioblastomas. Full article
(This article belongs to the Special Issue Novel Techniques and Technology for Treatment of Brain Tumors)
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15 pages, 5220 KiB  
Article
Differential Spatial Distribution of TSPO or Amino Acid PET Signal and MRI Contrast Enhancement in Gliomas
by Lena Kaiser, Adrien Holzgreve, Stefanie Quach, Michael Ingrisch, Marcus Unterrainer, Franziska J. Dekorsy, Simon Lindner, Viktoria Ruf, Julia Brosch-Lenz, Astrid Delker, Guido Böning, Bogdana Suchorska, Maximilian Niyazi, Christian H. Wetzel, Markus J. Riemenschneider, Sophia Stöcklein, Matthias Brendel, Rainer Rupprecht, Niklas Thon, Louisa von Baumgarten, Jörg-Christian Tonn, Peter Bartenstein, Sibylle Ziegler and Nathalie L. Albertadd Show full author list remove Hide full author list
Cancers 2022, 14(1), 53; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14010053 - 23 Dec 2021
Cited by 12 | Viewed by 2669
Abstract
In this study, dual PET and contrast enhanced MRI were combined to investigate their correlation per voxel in patients at initial diagnosis with suspected glioblastoma. Correlation with contrast enhancement (CE) as an indicator of BBB leakage was further used to evaluate whether PET [...] Read more.
In this study, dual PET and contrast enhanced MRI were combined to investigate their correlation per voxel in patients at initial diagnosis with suspected glioblastoma. Correlation with contrast enhancement (CE) as an indicator of BBB leakage was further used to evaluate whether PET signal is likely caused by BBB disruption alone, or rather attributable to specific binding after BBB passage. PET images with [18F]GE180 and the amino acid [18F]FET were acquired and normalized to healthy background (tumor-to-background ratio, TBR). Contrast enhanced images were normalized voxel by voxel with the pre-contrast T1-weighted MRI to generate relative CE values (rCE). Voxel-wise analysis revealed a high PET signal even within the sub-volumes without detectable CE. No to moderate correlation of rCE with TBR voxel-values and a small overlap as well as a larger distance of the hotspots delineated in rCE and TBR-PET images were detected. In contrast, voxel-wise correlation between both PET modalities was strong for most patients and hotspots showed a moderate overlap and distance. The high PET signal in tumor sub-volumes without CE observed in voxel-wise analysis as well as the discordant hotspots emphasize the specificity of the PET signals and the relevance of combined differential information from dual PET and MRI images. Full article
(This article belongs to the Special Issue Novel Techniques and Technology for Treatment of Brain Tumors)
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15 pages, 1259 KiB  
Article
Bilateral and Optimistic Warning Paradigms Improve the Predictive Power of Intraoperative Facial Motor Evoked Potentials during Vestibular Schwannoma Surgery
by Tobias Greve, Liang Wang, Sophie Katzendobler, Lucas L. Geyer, Christian Schichor, Jörg Christian Tonn and Andrea Szelényi
Cancers 2021, 13(24), 6196; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13246196 - 09 Dec 2021
Cited by 2 | Viewed by 1775
Abstract
Facial muscle corticobulbar motor evoked potentials (FMcoMEPs) are used to monitor facial nerve integrity during vestibular schwannoma resections to increase maximal safe tumor resection. Established warning criteria, based on ipsilateral amplitude reduction, have the limitation that the rate of false positive alarms is [...] Read more.
Facial muscle corticobulbar motor evoked potentials (FMcoMEPs) are used to monitor facial nerve integrity during vestibular schwannoma resections to increase maximal safe tumor resection. Established warning criteria, based on ipsilateral amplitude reduction, have the limitation that the rate of false positive alarms is high, in part because FMcoMEP changes occur on both sides, e.g., due to brain shift or pneumocephalus. We retrospectively compared the predictive value of ipsilateral-only warning criteria and actual intraoperative warnings with a novel candidate warning criterion, based on “ipsilateral versus contralateral difference in relative stimulation threshold increase, from baseline to end of resection” (BilatMT ≥ 20%), combined with an optimistic approach in which a warning would be triggered only if all facial muscles on the affected side deteriorated. We included 60 patients who underwent resection of vestibular schwannoma. The outcome variable was postoperative facial muscle function. Retrospectively applying BilatMT, with the optimistic approach, was found to have a significantly better false positive rate, which was much lower (9% at day 90) than the traditionally used ipsilateral warning criteria (>20%) and was also lower than actual intraoperative warnings. This is the first report combining the threshold method with an optimistic approach in a bilateral multi-facial muscle setup. This method could substantially reduce the rate of false positive alarms in FMcoMEP monitoring. Full article
(This article belongs to the Special Issue Novel Techniques and Technology for Treatment of Brain Tumors)
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21 pages, 2304 KiB  
Article
Effect of Varying Expression of EpCAM on the Efficiency of CTCs Detection by SERS-Based Immunomagnetic Optofluidic Device
by Marta Czaplicka, Krzysztof Niciński, Ariadna Nowicka, Tomasz Szymborski, Izabela Chmielewska, Joanna Trzcińska-Danielewicz, Agnieszka Girstun and Agnieszka Kamińska
Cancers 2020, 12(11), 3315; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12113315 - 10 Nov 2020
Cited by 13 | Viewed by 3061
Abstract
The circulating tumor cells (CTCs) isolation and characterization has a great potential for non-invasive biopsy. In the present research, the surface–enhanced Raman spectroscopy (SERS)-based assay utilizing magnetic nanoparticles and solid SERS-active support integrated in the external field assisted microfluidic device was designed for [...] Read more.
The circulating tumor cells (CTCs) isolation and characterization has a great potential for non-invasive biopsy. In the present research, the surface–enhanced Raman spectroscopy (SERS)-based assay utilizing magnetic nanoparticles and solid SERS-active support integrated in the external field assisted microfluidic device was designed for efficient isolation of CTCs from blood samples. Magnetic nanospheres (Fe2O3) were coated with SERS-active metal and then modified with p-mercaptobenzoic acid (p-MBA) which works simultaneously as a Raman reporter and linker to an antiepithelial-cell-adhesion-molecule (anti-EpCAM) antibodies. The newly developed laser-induced SERS-active silicon substrate with a very strong enhancement factor (up to 108) and high stability and reproducibility provide the additional extra-enhancement in the sandwich plasmonic configuration of immune assay which finally leads to increase the efficiency of detection. The sensitive immune recognition of cancer cells is assisted by the introducing of the controllable external magnetic field into the microfluidic chip. Moreover, the integration of the SERS-active platform and p-MBA-labeled immuno-Ag@Fe2O3 nanostructures with microfluidic device offers less sample and analytes demand, precise operation, increase reproducibly of spectral responses, and enables miniaturization and portability of the presented approach. In this work, we have also investigated the effect of varying expression of the EpCAM established by the Western Blot method supported by immunochemistry on the efficiency of CTCs’ detection with the developed SERS method. We used four target cancer cell lines with relatively high (human metastatic prostate adenocarcinoma cells (LNCaP)), medium (human metastatic prostate adenocarcinoma cells (LNCaP)), weak (human metastatic prostate adenocarcinoma cells (LNCaP)), and no EpCAM expressions (cervical cancer cells (HeLa)) to estimate the limits of detection based on constructed calibration curves. Finally, blood samples from lung cancer patients were used to validate the efficiency of the developed method in clinical trials. Full article
(This article belongs to the Special Issue Novel Techniques and Technology for Treatment of Brain Tumors)
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