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Article: Response assessment of GBM during immunotherapy by delayed contrast treatment response assessment maps.

Cuccarini, Valeria / Savoldi, Filippo / Mardor, Yael / Last, David / Pellegatta, Serena / Mazzi, Federica / Bruzzone, Maria Grazia / Anghileri, Elena / Pollo, Bianca / Maddaloni, Luisa / Russo, Camilla / Bocchi, Elisa / Pinzi, Valentina / Eoli, Marica / Aquino, Domenico

Frontiers in neurology

2024 Volume 15, Page(s) 1374737

Abstract: Introduction: Assessing the treatment response of glioblastoma multiforme during immunotherapy (IT) is an open issue. Treatment response assessment maps (TRAMs) might help distinguish true tumor progression (TTP) and pseudoprogression (PsP) in this ... ...

Abstract	Introduction: Assessing the treatment response of glioblastoma multiforme during immunotherapy (IT) is an open issue. Treatment response assessment maps (TRAMs) might help distinguish true tumor progression (TTP) and pseudoprogression (PsP) in this setting. Methods: We recruited 16 naïve glioblastoma patients enrolled in a phase II trial consisting of the Stupp protocol (a standardized treatment for glioblastoma involving combined radiotherapy and chemotherapy with temozolomide, followed by adjuvant temozolomide) plus IT with dendritic cells. Patients were followed up till progression or death; seven underwent a second surgery for suspected progression. Clinical, immunological, and MRI data were collected from all patients and histology in case of second surgery. Patients were classified as responders (progression-free survival, PFS > 12 months), and non-responders (PFS ≤ 12), HIGH-NK (natural killer cells, i.e., immunological responders), and LOW-NK (immunological non-responders) based on immune cell counts in peripheral blood. TRAMs differentiate contrast-enhancing lesions with different washout dynamics into hypothesized tumoral (conventionally blue-colored) vs. treatment-related (red-colored). Results: Using receiver operating characteristic (ROC) curves, a threshold of -0.066 in V Discussion: In conclusion, in our pilot study TRAMs support the discrimination between tumoral and treatment-related enhancing features in immunological responders vs. non-responders, the distinction between PsP and TTP, and might provide surrogate markers of immunological response.
Language	English
Publishing date	2024-04-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2024.1374737
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Article ; Online: Prospective Analysis of Radiation-Induced Contrast Enhancement and Health-Related Quality of Life After Proton Therapy for Central Nervous System and Skull Base Tumors.

Lütgendorf-Caucig, Carola / Pelak, Maciej / Hug, Eugen / Flechl, Birgit / Surböck, Birgit / Marosi, Christine / Mock, Ulrike / Zach, Leor / Mardor, Yael / Furman, Orit / Hentschel, Harald / Gora, Joanna / Fossati, Piero / Stock, Markus / Graichen, Uwe / Klee, Sascha / Georg, Petra

International journal of radiation oncology, biology, physics

2024 Volume 118, Issue 5, Page(s) 1206–1216

Abstract: Purpose: Intracerebral radiation-induced contrast enhancement (RICE) can occur after photon as well as proton beam therapy (PBT). This study evaluated the incidence, characteristics, and risk factors of RICE after PBT delivered to, or in direct ... ...

Abstract	Purpose: Intracerebral radiation-induced contrast enhancement (RICE) can occur after photon as well as proton beam therapy (PBT). This study evaluated the incidence, characteristics, and risk factors of RICE after PBT delivered to, or in direct proximity to, the brain and its effect on health-related quality of life (HRQoL). Methods and materials: Four hundred twenty-one patients treated with pencil beam scanning PBT between 2017 and 2021 were included. Follow-up included clinical evaluation and contrast-enhanced magnetic resonance imaging at 3, 6, and 12 months after treatment completion and annually thereafter. RICE was graded according to Common Terminology Criteria for Adverse Events version 4, and HRQoL parameters were assessed via European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 questionnaires. Results: The median follow-up was 24 months (range, 6-54), and median dose to 1% relative volume of noninvolved central nervous system (D1%CNS) was 54.3 Gy relative biologic effectiveness (RBE; range, 30-76 Gy RBE). The cumulative RICE incidence was 15% (n = 63), of which 10.5% (n = 44) were grade 1, 3.1% (n = 13) were grade 2, and 1.4% (n = 6) were grade 3. No grade 4 or 5 events were observed. Twenty-six of 63 RICE (41.3%) had resolved at the latest follow-up. The median onset after PBT and duration of RICE in patients in whom the lesions resolved were 11.8 and 9.0 months, respectively. On multivariable analysis, D1%CNS > 57.6 Gy RBE, previous in-field radiation, and diabetes mellitus were identified as significant risk factors for RICE development. Previous radiation was the only factor influencing the risk of symptomatic RICE. After PBT, general HRQoL parameters were not compromised. In a matched cohort analysis of 54/50 patients with and without RICE, no differences in global health score or functional and symptom scales were seen. Conclusions: The overall incidence of clinically relevant RICE after PBT is very low and has no significant negative effect on long-term patient QoL.
MeSH term(s)	Humans ; Proton Therapy/adverse effects ; Proton Therapy/methods ; Skull Base Neoplasms/diagnostic imaging ; Skull Base Neoplasms/radiotherapy ; Quality of Life ; Radiation Injuries/pathology ; Radiotherapy Dosage ; Brain/radiation effects
Language	English
Publishing date	2024-01-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	197614-x
ISSN	1879-355X ; 0360-3016
ISSN (online)	1879-355X
ISSN	0360-3016
DOI	10.1016/j.ijrobp.2024.01.007
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Zs.A 1218: Show issues

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Article ; Online: Abdominal fat depots are related to lower cognitive functioning and brain volumes in middle-aged males at high Alzheimer's risk.

Golan Shekhtman, Sapir / Boccara, Ethel / Ravona-Springer, Ramit / Inbar, Yael / Zelicha, Hila / Livny, Abigail / Bendlin, Barbara B / Lesman-Segev, Orit / Yore, Iscka / Heymann, Anthony / Sano, Mary / Mardor, Yael / Azuri, Joseph / Schnaider Beeri, Michal

Obesity (Silver Spring, Md.)

2024 Volume 32, Issue 5, Page(s) 1009–1022

Abstract: Objective: High BMI, which poorly represents specific fat depots, is linked to poorer cognition and higher dementia risk, with different associations between sexes. This study examined associations of abdominal fat depots with cognition and brain ... ...

Abstract	Objective: High BMI, which poorly represents specific fat depots, is linked to poorer cognition and higher dementia risk, with different associations between sexes. This study examined associations of abdominal fat depots with cognition and brain volumes and whether sex modifies this association. Methods: A total of 204 healthy middle-aged offspring of Alzheimer's dementia patients (mean age = 59.44, 60% females) underwent abdominal magnetic resonance imaging to quantify hepatic, pancreatic, visceral, and subcutaneous adipose tissue and to assess cognition and brain volumes. Results: In the whole sample, higher hepatic fat percentage was associated with lower total gray matter volume (β = -0.17, p < 0.01). Primarily in males, higher pancreatic fat percentage was associated with lower global cognition (males: β = -0.27, p = 0.03; females: β = 0.01, p = 0.93) executive function (males: β = -0.27, p = 0.03; females: β = 0.02, p = 0.87), episodic memory (males: β = -0.28, p = 0.03; females: β = 0.07, p = 0.48), and inferior frontal gyrus volume (males: β = -0.28, p = 0.02; females: β = 0.10, p = 0.33). Visceral and subcutaneous adipose tissue was inversely associated with middle frontal and superior frontal gyrus volumes in males and females. Conclusions: In middle-aged males at high Alzheimer's dementia risk, but not in females, higher pancreatic fat was associated with lower cognition and brain volumes. These findings suggest a potential sex-specific link between distinct abdominal fat with brain health.
MeSH term(s)	Humans ; Male ; Alzheimer Disease/diagnostic imaging ; Female ; Middle Aged ; Brain/diagnostic imaging ; Brain/pathology ; Magnetic Resonance Imaging ; Cognition ; Abdominal Fat/diagnostic imaging ; Abdominal Fat/pathology ; Aged ; Body Mass Index ; Risk Factors ; Sex Factors ; Gray Matter/diagnostic imaging ; Gray Matter/pathology ; Pancreas/pathology ; Pancreas/diagnostic imaging ; Organ Size
Language	English
Publishing date	2024-02-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2230457-5
ISSN	1930-739X ; 1071-7323 ; 1930-7381
ISSN (online)	1930-739X
ISSN	1071-7323 ; 1930-7381
DOI	10.1002/oby.24004
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Zs.A 4061: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: The effects of point-source electroporation on the blood-brain barrier and brain vasculature in rats: An MRI and histology study.

Sharabi, Shirley / Last, David / Daniels, Dianne / Liraz Zaltsman, Sigal / Mardor, Yael

Bioelectrochemistry (Amsterdam, Netherlands)

2020 Volume 134, Page(s) 107521

Abstract: When applying electroporation to the brain, it is important to understand the effects on the blood-brain barrier (BBB) and brain vasculature. Here we studied the effects of point-source electroporation on rats' brains as a function of time from treatment ...

Abstract	When applying electroporation to the brain, it is important to understand the effects on the blood-brain barrier (BBB) and brain vasculature. Here we studied the effects of point-source electroporation on rats' brains as a function of time from treatment using conventional contrast-enhanced MRI and treatment response assessment maps (TRAMs), enabling depiction of subtle BBB disruption and differentiating contrast agent clearance from accumulation. Effects on vessels were also studied using Lectin staining. The TRAMs revealed that conventional contrast-enhanced MRI underestimates BBB disruption volume by nearly a factor of two, and that despite significant enhancement on standard MRI immediately post electroporation, there was no contrast accumulation in the tissue (clearance was faster than accumulation). Histology revealed significant increased vessel coverage in the treated striatum (40 ± 24% p < 0.03) immediately post electroporation, suggesting vasodilatation. Two-three hours post electroporation, both conventional MRI and TRAMs showed minor BBB disruption and histology showed decreased vessel coverage (56 ± 16%, p < 0.01), suggesting vasoconstriction. Four hours post electroporation, despite minor enhancement, the TRAMs showed significant BBB disruption with contrast accumulation, lasting over 24 h, with decreasing volumes. These results suggest that electroporation triggers several unique brain vascular mechanisms and that the optimal time window for drug administration is 4-6 h after electroporation.
MeSH term(s)	Animals ; Blood-Brain Barrier/cytology ; Blood-Brain Barrier/diagnostic imaging ; Blood-Brain Barrier/metabolism ; Brain/blood supply ; Brain/cytology ; Brain/diagnostic imaging ; Brain/metabolism ; Electroporation ; Magnetic Resonance Imaging ; Male ; Rats
Language	English
Publishing date	2020-03-31
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2010650-6
ISSN	1878-562X ; 0302-4598 ; 1567-5394
ISSN (online)	1878-562X
ISSN	0302-4598 ; 1567-5394
DOI	10.1016/j.bioelechem.2020.107521
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Zs.A 1178: Show issues

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Article ; Online: BBB opening by low pulsed electric fields, depicted by delayed-contrast MRI, enables efficient delivery of therapeutic doxorubicin doses into mice brains.

Cooper, Itzik / Last, David / Ravid, Orly / Rand, Daniel / Matsree, Erez / Omesi, Liora / Shemesh, Chen / Liberman, Meir / Zach, Leor / Furman, Orit / Daniels, Dianne / Liraz-Zaltsman, Sigal / Mardor, Yael / Sharabi, Shirley

Fluids and barriers of the CNS

2023 Volume 20, Issue 1, Page(s) 67

Abstract: Background: Pharmacological treatment of CNS diseases is limited due to the presence of the blood-brain barrier (BBB). Recent years showed significant advancement in the field of CNS drug delivery enablers, with technologies such as MR-guided focused ... ...

Abstract	Background: Pharmacological treatment of CNS diseases is limited due to the presence of the blood-brain barrier (BBB). Recent years showed significant advancement in the field of CNS drug delivery enablers, with technologies such as MR-guided focused ultrasound reaching clinical trials. This have inspired researchers in the field to invent novel brain barriers opening (BBo) technologies that are required to be simple, fast, safe and efficient. One such technology, recently developed by us, is BDF (Barrier Disrupting Fields), based on low pulsed electric fields (L-PEFs) for opening the BBB in a controlled, safe, reversible and non-invasive manner. Here, we conducted an in vivo study to show that BDF is a feasible technology for delivering Doxorubicin (Doxo) into mice brain. Means for depicting BBBo levels were developed and applied for monitoring the treatment and predicting response. Overall, the goals of the presented study were to demonstrate the feasibility for delivering therapeutic Doxo doses into naïve and tumor-bearing mice brains and applying delayed-contrast MRI (DCM) for monitoring the levels of BBBo. Methods: L-PEFs were applied using plate electrodes placed on the intact skull of naïve mice. L-PEFs/Sham mice were scanned immediately after the procedure by DCM ("MRI experiment"), or injected with Doxo and Trypan blue followed by delayed (4 h) perfusion and brain extraction ("Doxo experiment"). Doxo concentrations were measured in brain samples using confocal microscopy and compared to IC Results: Significant amount of Doxo was found in cortical regions of all L-PEFs-treated mice brains (0.50 ± 0.06 µg Doxo/gr brain) while in Sham brains, Doxo concentrations were below or on the verge of detection limit (0.03 ± 0.02 µg Doxo/gr brain). This concentration was x97 higher than IC Conclusions: Our results demonstrate significant BBBo levels induced by extra-cranial L-PEFs, enabling efficient delivery of therapeutic Doxo doses into the brain and reducing tumor growth. As BBBo was undetectable by standard contrast-enhanced MRI, DCM was applied to generate maps depicting the BBBo levels throughout the brain. These findings suggest that BDF is a promising technology for efficient drug delivery into the brain with important implications for future treatment of brain cancer and additional CNS diseases.
MeSH term(s)	Humans ; Animals ; Mice ; Blood-Brain Barrier ; Mice, Nude ; Brain/diagnostic imaging ; Brain Neoplasms/diagnostic imaging ; Brain Neoplasms/drug therapy ; Glioma/diagnostic imaging ; Glioma/drug therapy ; Doxorubicin/pharmacology
Chemical Substances	Doxorubicin (80168379AG)
Language	English
Publishing date	2023-09-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2595406-4
ISSN	2045-8118 ; 2045-8118
ISSN (online)	2045-8118
ISSN	2045-8118
DOI	10.1186/s12987-023-00468-7
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Article: Non-Invasive Low Pulsed Electrical Fields for Inducing BBB Disruption in Mice-Feasibility Demonstration.

Sharabi, Shirley / Last, David / Daniels, Dianne / Fabian, Ido Didi / Atrakchi, Dana / Bresler, Yael / Liraz-Zaltsman, Sigal / Cooper, Itzik / Mardor, Yael

Pharmaceutics

2021 Volume 13, Issue 2

Abstract: The blood-brain barrier (BBB) is a major hurdle for the treatment of central nervous system disorders, limiting passage of both small and large therapeutic agents from the blood stream into the brain. Thus, means for inducing BBB disruption (BBBd) are ... ...

Abstract	The blood-brain barrier (BBB) is a major hurdle for the treatment of central nervous system disorders, limiting passage of both small and large therapeutic agents from the blood stream into the brain. Thus, means for inducing BBB disruption (BBBd) are urgently needed. Here, we studied the application of low pulsed electrical fields (PEFs) for inducing BBBd in mice. Mice were treated by low PEFs using electrodes pressed against both sides of the skull (100-400 square 50 µs pulses at 4 Hz with different voltages). BBBd as a function of treatment parameters was evaluated using MRI-based treatment response assessment maps (TRAMs) and Evans blue extravasation. A 3D numerical model of the mouse brain and electrodes was constructed using finite element software, simulating the electric fields distribution in the brain and ensuring no significant temperature elevation. BBBd was demonstrated immediately after treatment and significant linear regressions were found between treatment parameters and the extent of BBBd. The maximal induced electric field in the mice brains, calculated by the numerical model, ranged between 62.4 and 187.2 V/cm for the minimal and maximal applied voltages. These results demonstrate the feasibility of inducing significant BBBd using non-invasive low PEFs, well below the threshold for electroporation.
Language	English
Publishing date	2021-01-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics13020169
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Article ; Online: Reply.

Moisseiev, Elad / Barak, Adiel / Mardor, Yael

Retina (Philadelphia, Pa.)

2016 Volume 36, Issue 5, Page(s) e40

Language	English
Publishing date	2016-05
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	603192-4
ISSN	1539-2864 ; 0275-004X
ISSN (online)	1539-2864
ISSN	0275-004X
DOI	10.1097/IAE.0000000000001057
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Zs.A 1724: Show issues

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Article ; Online: Application of Delayed Contrast Extravasation Magnetic Resonance Imaging for Depicting Subtle Blood-Brain Barrier Disruption in a Traumatic Brain Injury Model.

Liraz Zaltsman, Sigal / Sharabi, Shirley / Guez, David / Daniels, Diann / Cooper, Itzik / Shemesh, Chen / Atrakchi, Dana / Ravid, Orly / Omesi, Liora / Rand, Daniel / Livny, Abigail / Schnaider Beeri, Michal / Friedman-Levi, Yael / Shohami, Esther / Mardor, Yael / Last, David

Journal of neurotrauma

2023 Volume 41, Issue 3-4, Page(s) 430–446

Abstract: The blood-brain barrier (BBB) is composed of brain microvasculature that provides selective transport of solutes from the systemic circulation into the central nervous system to protect the brain and spinal microenvironment. Damage to the BBB in the ... ...

Abstract	The blood-brain barrier (BBB) is composed of brain microvasculature that provides selective transport of solutes from the systemic circulation into the central nervous system to protect the brain and spinal microenvironment. Damage to the BBB in the acute phase after traumatic brain injury (TBI) is recognized as a major underlying mechanism leading to secondary long-term damage. Because of the lack of technological ability to detect subtle BBB disruption (BBBd) in the chronic phase, however, the presence of chronic BBBd is disputable. Thus, the dynamics and course of long-term BBBd post-TBI remains elusive. Thirty C57BL/6 male mice subjected to TBI using our weight drop closed head injury model and 19 naïve controls were scanned by magnetic resonance imaging (MRI) up to 540 days after injury. The BBB maps were calculated from delayed contrast extravasation MRI (DCM) with high spatial resolution and high sensitivity to subtle BBBd, enabling depiction and quantification of BBB permeability. At each time point, 2-6 animals were sacrificed and their brains were extracted, sectioned, and stained for BBB biomarkers including: blood microvessel coverage by astrocyte using GFAP, AQP4, ZO-1 gaps, and IgG leakage. We found that DCM provided depiction of subtle yet significant BBBd up to 1.5 years after TBI, with significantly higher sensitivity than standard contrast-enhanced T1-weighted and T2-weighted MRI (BBBd volumes main effect DCM/T1/T2
MeSH term(s)	Male ; Animals ; Mice ; Blood-Brain Barrier/diagnostic imaging ; Mice, Inbred C57BL ; Brain/blood supply ; Magnetic Resonance Imaging/methods ; Brain Injuries, Traumatic/diagnostic imaging
Language	English
Publishing date	2023-12-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	645092-1
ISSN	1557-9042 ; 0897-7151
ISSN (online)	1557-9042
ISSN	0897-7151
DOI	10.1089/neu.2023.0048
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Zs.A 2016: Show issues

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Article ; Online: Synthesis and preliminary biological evaluation of gabactyzine, a benactyzine-GABA mutual prodrug, as an organophosphate antidote.

Weitman, Michal / Eisenkraft, Arik / TaShma, Zeev / Makarovsky, Igor / Last, David / Daniels, Dianne / Guez, David / Shneor, Ran / Mardor, Yael / Nudelman, Abraham / Krivoy, Amir

Scientific reports

2022 Volume 12, Issue 1, Page(s) 18078

Abstract: Organophosphates (OPs) are inhibitors of acetylcholinesterase and have deleterious effects on the central nervous system. Clinical manifestations of OP poisoning include convulsions, which represent an underlying toxic neuro-pathological process, leading ...

Abstract	Organophosphates (OPs) are inhibitors of acetylcholinesterase and have deleterious effects on the central nervous system. Clinical manifestations of OP poisoning include convulsions, which represent an underlying toxic neuro-pathological process, leading to permanent neuronal damage. This neurotoxicity is mediated through the cholinergic, GABAergic and glutamatergic (NMDA) systems. Pharmacological interventions in OP poisoning are designed to mitigate these specific neuro-pathological pathways, using anticholinergic drugs and GABAergic agents. Benactyzine is a combined anticholinergic, anti-NMDA compound. Based on previous development of novel GABA derivatives (such as prodrugs based on perphenazine for the treatment of schizophrenia and nortriptyline against neuropathic pain), we describe the synthesis and preliminary testing of a mutual prodrug ester of benactyzine and GABA. It is assumed that once the ester crosses the blood-brain-barrier it will undergo hydrolysis, releasing benactyzine and GABA, which are expected to act synergistically. The combined release of both compounds in the brain offers several advantages over the current OP poisoning treatment protocol: improved efficacy and safety profile (where the inhibitory properties of GABA are expected to counteract the anticholinergic cognitive adverse effects of benactyzine) and enhanced chemical stability compared to benactyzine alone. We present here preliminary results of animal studies, showing promising results with early gabactyzine administration.
MeSH term(s)	Animals ; Benactyzine ; Antidotes/therapeutic use ; Prodrugs/pharmacology ; Prodrugs/therapeutic use ; Organophosphates ; Acetylcholinesterase/metabolism ; Chemical Warfare Agents ; Cholinergic Antagonists/pharmacology ; Esters ; gamma-Aminobutyric Acid ; Organophosphate Poisoning/drug therapy ; Cholinesterase Inhibitors/pharmacology
Chemical Substances	Benactyzine (595EG71R3F) ; Antidotes ; Prodrugs ; Organophosphates ; Acetylcholinesterase (EC 3.1.1.7) ; Chemical Warfare Agents ; Cholinergic Antagonists ; Esters ; gamma-Aminobutyric Acid (56-12-2) ; Cholinesterase Inhibitors
Language	English
Publishing date	2022-10-27
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-23141-9
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Article ; Online: The application of point source electroporation and chemotherapy for the treatment of glioma: a randomized controlled rat study.

Sharabi, Shirley / Guez, David / Daniels, Dianne / Cooper, Itzik / Atrakchi, Dana / Liraz-Zaltsman, Sigal / Last, David / Mardor, Yael

Scientific reports

2020 Volume 10, Issue 1, Page(s) 2178

Abstract: The prognosis of Glioblastoma Multiforme patients is poor despite aggressive therapy. Reasons include poor chemotherapy penetration across the blood-brain barrier and tumor infiltration into surrounding tissues. Here we studied the effects of combined ... ...

Abstract	The prognosis of Glioblastoma Multiforme patients is poor despite aggressive therapy. Reasons include poor chemotherapy penetration across the blood-brain barrier and tumor infiltration into surrounding tissues. Here we studied the effects of combined point-source electroporation (EP) and systemic chemotherapy in glioma-bearing rats. 128 rats were studied. Treatment groups were administered systemic Cisplatin/Methotrexate before EP (either 90 or 180 pulses). Control groups were treated by EP, chemotherapy, or no treatment. Tumor volumes were determined by MRI. Tumors growth rates of the EP + Methotrexate group (1.02 ± 0.77) were significantly lower (p < 0.01) than the control (5.2 ± 1.0) 1-week post treatment. No significant difference was found compared to Methotrexate (1.7 ± 0.5). Objective response rates (ORR) were 40% and 57% for the Methotrexate and EP + Methotrexate groups respectively. Tumor growth rates and ORR of the EP + Cisplatin groups (90 pulses 0.98 ± 0.2, 57%, 180 pulses 1.2 ± 0.1, 33%) were significantly smaller than the control (6.4 ± 1.0, p < 0.01, p < 0.02, 0%) and Cisplatin (3.9 ± 1.0, p < 0.04, p < 0.05, 13%) groups. No significant differences were found between the control groups. Increased survival was found in the EP + Cisplatin group, Χ
MeSH term(s)	Animals ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/therapeutic use ; Brain Neoplasms/drug therapy ; Cell Line, Tumor ; Cisplatin/administration & dosage ; Cisplatin/therapeutic use ; Electroporation/instrumentation ; Electroporation/methods ; Glioma/drug therapy ; Male ; Methotrexate/administration & dosage ; Methotrexate/therapeutic use ; Random Allocation ; Rats ; Rats, Inbred Lew
Chemical Substances	Antineoplastic Agents ; Cisplatin (Q20Q21Q62J) ; Methotrexate (YL5FZ2Y5U1)
Language	English
Publishing date	2020-02-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-59152-7
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