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Moroşan GC, Moroşan AC, Ionescu C, Sava A. Neuropsychiatric symptoms as early indicators of brain tumors. Arch Clin Cases 2024; 11:120-126. [PMID: 39712552 PMCID: PMC11661549 DOI: 10.22551/2024.45.1104.10302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2024] Open
Abstract
Brain tumors, despite the high mortality and morbidity, they are a rare type of heterogenous tumors that are highly dependent on sex, age, race, level of education, and socioeconomic status. Due to their high mortality rates, it is important to identify as many potential biomarkers for early detection as the earlier the tumor is discovered, the better the prognosis. One such early biomarker we propose in the current paper is the assessment of anxiety, depression, and cognitive changes. In most cancer patients, a certain degree of anxiety and depression is expected upon receiving the diagnosis as it triggers fears regarding the prognosis, possible side effects of the treatment, and even the possibility of the treatment failing. In this paper we analyzed the way anxiety, depression, and cognitive changes present themselves in the case of several types of tumors and whether these could be used as early markers. We have observed that most of the cognitive changes present are due to the location, size, and type of the tumor with some highly connected to anxiety and depression. Moreover, in the case of certain tumors, the removal of the mass has not improved the mood or cognitive function.
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Affiliation(s)
- George-Cătălin Moroşan
- Department of Morpho-Functional Sciences I, Grigore T. Popa University Medicine and Pharmacy, Iasi, Romania
| | | | - Cătălina Ionescu
- Department of Biology, Faculty of Biology, Alexandru Ioan Cuza University, Iasi, Romania
| | - Anca Sava
- Department of Morpho-Functional Sciences I, Grigore T. Popa University Medicine and Pharmacy, Iasi, Romania
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Bai F, Deng Y, Li L, Lv M, Razzokov J, Xu Q, Xu Z, Chen Z, Chen G, Chen Z. Advancements and challenges in brain cancer therapeutics. EXPLORATION (BEIJING, CHINA) 2024; 4:20230177. [PMID: 39713205 PMCID: PMC11655316 DOI: 10.1002/exp.20230177] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Accepted: 04/02/2024] [Indexed: 12/24/2024]
Abstract
Treating brain tumors requires a nuanced understanding of the brain, a vital and delicate organ. Location, size, tumor type, and surrounding tissue health are crucial in developing treatment plans. This review comprehensively summarizes various treatment options that are available or could be potentially available for brain tumors, including physical therapies (radiotherapy, ablation therapy, photodynamic therapy, tumor-treating field therapy, and cold atmospheric plasma therapy) and non-physical therapies (surgical resection, chemotherapy, targeted therapy, and immunotherapy). Mechanisms of action, potential side effects, indications, and latest developments, as well as their limitations, are highlighted. Furthermore, the requirements for personalized, multi-modal treatment approaches in this rapidly evolving field are discussed, emphasizing the balance between efficacy and patient safety.
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Affiliation(s)
- Fan Bai
- Paul C Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health EngineeringShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenChina
- Advanced Therapeutic CenterNational Innovation Center for Advanced Medical DevicesShenzhenChina
| | - Yueyang Deng
- Department of Biomedical EngineeringMcGill UniversityMontrealQuebecCanada
- Rosalind & Morris Goodman Cancer InstituteMcGill UniversityMontrealQuebecCanada
| | - Long Li
- Paul C Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health EngineeringShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenChina
- University of Chinese Academy of SciencesShenzhenGuangdongP. R. China
| | - Ming Lv
- Department of Medical EngineeringMedical Supplies Center of Chinese PLA General HospitalBeijingChina
| | - Jamoliddin Razzokov
- Institute of Fundamental and Applied ResearchNational Research University TIIAMETashkentUzbekistan
- Laboratory of Experimental BiophysicsCentre for Advanced TechnologiesTashkentUzbekistan
- Department of Biomedical EngineeringTashkent State Technical UniversityTashkentUzbekistan
| | - Qingnan Xu
- Paul C Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health EngineeringShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenChina
| | - Zhen Xu
- Paul C Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health EngineeringShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenChina
| | - Zhaowei Chen
- Institute of Food Safety and Environment MonitoringMOE Key Laboratory for Analytical Science of Food Safety and BiologyCollege of ChemistryFuzhou UniversityFuzhouChina
| | - Guojun Chen
- Department of Biomedical EngineeringMcGill UniversityMontrealQuebecCanada
- Rosalind & Morris Goodman Cancer InstituteMcGill UniversityMontrealQuebecCanada
| | - Zhitong Chen
- Paul C Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health EngineeringShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenChina
- Advanced Therapeutic CenterNational Innovation Center for Advanced Medical DevicesShenzhenChina
- University of Chinese Academy of SciencesShenzhenGuangdongP. R. China
- Key Laboratory of Biomedical Imaging Science and SystemChinese Academy of SciencesShenzhenChina
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Li J, Sun W, Hu S, Yan X. The Implication of Photodynamic Therapy Applied to the Level of Tumor Resection on Postoperative Cerebral Edema and Intracranial Pressure Changes in Gliomas. Lasers Surg Med 2024; 56:709-722. [PMID: 39256928 DOI: 10.1002/lsm.23837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Revised: 08/17/2024] [Accepted: 08/19/2024] [Indexed: 09/12/2024]
Abstract
AIM The aim of our study was to explore the factors influencing cerebral edema and intracranial pressure in glioblastoma multiforme (GBM) patients who undergo photodynamic therapy (PDT) after resection. APPROACH This was a retrospective controlled study of GBM patients treated with PDT-assisted resections of varying scope from May 2021 to August 2023. The baseline clinical data, cerebral edema volumes, intracranial pressure values, and imaging data of the GBM patients were collected for statistical analysis. RESULTS A total of 56 GBM patients were included. Thirty of the patients underwent gross total resection (GTR), and the other 26 patients underwent subtotal resection (STR). We found that the cerebral edema volume and the mean intracranial pressure in patients who underwent GTR were lower than those in patients who underwent STR. Moreover, univariate analysis showed that the scope of tumor resection was an independent factor affecting cerebral edema and intracranial pressure after PDT. CONCLUSIONS Compared with STR, PDT combined with GTR significantly reduced postoperative brain edema volume and intracranial pressure in GBM patients.
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Affiliation(s)
- Jingxuan Li
- Department of Neurosurgery, Cancer Center, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Weijun Sun
- Department of Neurosurgery, Cancer Center, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Shaoshan Hu
- Department of Neurosurgery, Cancer Center, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Xiuwei Yan
- Department of Neurosurgery, Cancer Center, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
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Arpa A, Yigit A, Basar I, Yilmaz T. The Effect of Hydrocephalus on the Optic Nerve in the Presence of Intracranial Mass. World Neurosurg 2024; 187:e656-e664. [PMID: 38704142 DOI: 10.1016/j.wneu.2024.04.142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 04/23/2024] [Indexed: 05/06/2024]
Abstract
OBJECTIVE The measurement of optic nerve sheath diameter is a noninvasive, practical, and economical method used to identify increased intracranial pressure. The purpose of this study is to detect the preoperative and postoperative changes in optic nerve sheath diameter in patients with intracranial mass, to correlate these changes with optic nerve diameter variations, and to evaluate the impact of hydrocephalus on these alterations. MATERIAL AND METHOD This study was conducted with patients who presented to our clinic with complaints of intracranial mass, were decided for surgery, and underwent surgical procedures. FINDINGS The optic nerve and optic nerve sheath diameter measurement values were different preoperatively and postoperatively, with a significant decrease in the optic nerve sheath diameter in all groups in postoperative measurements, while the optic nerve diameter significantly increased. CONCLUSIONS Although there was no significant difference between the effects of hydrocephalus and intracranial mass-related increase in intracranial pressure on the optic nerve and optic nerve sheath, it was observed that hydrocephalus increased intracranial pressure when considering the Evans ratio. It has been determined that as ventricular dilatation increases, so does intracranial pressure, which leads to an increase in the diameter of the optic nerve sheath, resulting in papilledema and thinning of the optic nerve. These findings indicate the importance of early cerebrospinal fluid diversion and monitoring optic nerve sheath diameter in the management.
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Affiliation(s)
- Abdurrahman Arpa
- Department of Neurosurgery, Dicle University School of Medicine, Diyarbakir, Turkey.
| | - Abdullah Yigit
- Department of Neurosurgery, Dicle University School of Medicine, Diyarbakir, Turkey
| | - Ibrahim Basar
- Department of Neurosurgery, Dicle University School of Medicine, Diyarbakir, Turkey
| | - Tevfik Yilmaz
- Department of Neurosurgery, Dicle University School of Medicine, Diyarbakir, Turkey
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Guo B, Cao N, Zhang R, Yang P. GETNet: Group Normalization Shuffle and Enhanced Channel Self-Attention Network Based on VT-UNet for Brain Tumor Segmentation. Diagnostics (Basel) 2024; 14:1257. [PMID: 38928672 PMCID: PMC11203032 DOI: 10.3390/diagnostics14121257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Revised: 06/08/2024] [Accepted: 06/11/2024] [Indexed: 06/28/2024] Open
Abstract
Currently, brain tumors are extremely harmful and prevalent. Deep learning technologies, including CNNs, UNet, and Transformer, have been applied in brain tumor segmentation for many years and have achieved some success. However, traditional CNNs and UNet capture insufficient global information, and Transformer cannot provide sufficient local information. Fusing the global information from Transformer with the local information of convolutions is an important step toward improving brain tumor segmentation. We propose the Group Normalization Shuffle and Enhanced Channel Self-Attention Network (GETNet), a network combining the pure Transformer structure with convolution operations based on VT-UNet, which considers both global and local information. The network includes the proposed group normalization shuffle block (GNS) and enhanced channel self-attention block (ECSA). The GNS is used after the VT Encoder Block and before the downsampling block to improve information extraction. An ECSA module is added to the bottleneck layer to utilize the characteristics of the detailed features in the bottom layer effectively. We also conducted experiments on the BraTS2021 dataset to demonstrate the performance of our network. The Dice coefficient (Dice) score results show that the values for the regions of the whole tumor (WT), tumor core (TC), and enhancing tumor (ET) were 91.77, 86.03, and 83.64, respectively. The results show that the proposed model achieves state-of-the-art performance compared with more than eleven benchmarks.
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Affiliation(s)
- Bin Guo
- College of Information Science and Engineering, Hohai University, Nanjing 210098, China;
- College of Computer and Information Engineering, Xinjiang Agricultural University, Urumqi 830052, China; (R.Z.); (P.Y.)
| | - Ning Cao
- College of Information Science and Engineering, Hohai University, Nanjing 210098, China;
| | - Ruihao Zhang
- College of Computer and Information Engineering, Xinjiang Agricultural University, Urumqi 830052, China; (R.Z.); (P.Y.)
| | - Peng Yang
- College of Computer and Information Engineering, Xinjiang Agricultural University, Urumqi 830052, China; (R.Z.); (P.Y.)
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Zeng J, Moore NJ. A Computational Framework for the Administration of 5-Aminovulinic Acid Before Glioblastoma Surgery. Bull Math Biol 2024; 86:83. [PMID: 38842602 DOI: 10.1007/s11538-024-01312-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Accepted: 05/24/2024] [Indexed: 06/07/2024]
Abstract
5-Aminolevulinic Acid (5-ALA) is the only fluorophore approved by the FDA as an intraoperative optical imaging agent for fluorescence-guided surgery in patients with glioblastoma. The dosing regimen is based on rodent tests where a maximum signal occurs around 6 h after drug administration. Here, we construct a computational framework to simulate the transport of 5-ALA through the stomach, blood, and brain, and the subsequent conversion to the fluorescent agent protoporphyrin IX at the tumor site. The framework combines compartmental models with spatially-resolved partial differential equations, enabling one to address questions regarding quantity and timing of 5-ALA administration before surgery. Numerical tests in two spatial dimensions indicate that, for tumors exceeding the detection threshold, the time to peak fluorescent concentration is 2-7 h, broadly consistent with the current surgical guidelines. Moreover, the framework enables one to examine the specific effects of tumor size and location on the required dose and timing of 5-ALA administration before glioblastoma surgery.
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Affiliation(s)
- Jia Zeng
- Colgate University, Hamilton, USA
- Harvard University, Cambridge, USA
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Sun T, Mei N, Su Y, Shan S, Qian W, Li M, Zhang Z. Mendelian randomization combined with multi-omics explores the relationship between heart failure and cancer. J Cancer 2024; 15:2928-2939. [PMID: 38706896 PMCID: PMC11064263 DOI: 10.7150/jca.94142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Accepted: 02/27/2024] [Indexed: 05/07/2024] Open
Abstract
Background: Whether there is an association between HF (HF) and cancer has not been conclusively established, and it is not clear whether patients with cancer can share similar hospitalization strategies and outcomes with patients with HF. Methods: Genome-wide association summary statistics were performed using a two-sample Mendelian randomization (MR) method for HF patients and cancer patients from the GWAS directory, with co-localization and Summary Data-Based Mendelian Randomization (SMR) analyses to identify HF-associated genes, and transcriptomic analyses to analyze the roles of these genes in the clinical diagnosis and targeted therapies of multiple cancer types. Results: Two-sample MR analysis showed that increased risk of HF was associated with decreased risk of cervical, brain, breast, colorectal, lung, and skin cancers, and co-localization combined with SMR analysis identified ABO and SURF1 as HF-associated genes, and transcriptomic analyses showed that ABO is a risk factor for HF and a protective factor against cancer, whereas SURF1 is a protective factor against HF and a protective factor against cancer. Conclusion: There was no causal relationship between heart failure and cancers (Cervical, brain, breast, colorectal, lung and skin cancers) risk factors, however there was a trend toward a negative causal relationship between heart failure and cancers (Cervical, brain, breast, colorectal, lung and skin cancers) occurrence.
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Affiliation(s)
- Tian Sun
- Hubei provincial key laboratory of diabetic cardiovascular diseases, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, Hubei, People's Republic of China
- School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, Hubei University of Science and Technology, Xianning 437100, Hubei, People's Republic of China
- School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, Hubei, People's Republic of China
| | - Na Mei
- Hubei provincial key laboratory of diabetic cardiovascular diseases, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, Hubei, People's Republic of China
- School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, Hubei University of Science and Technology, Xianning 437100, Hubei, People's Republic of China
| | - Yanting Su
- School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, Hubei University of Science and Technology, Xianning 437100, Hubei, People's Republic of China
| | - Shigang Shan
- School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, Hubei University of Science and Technology, Xianning 437100, Hubei, People's Republic of China
| | - Wenbin Qian
- School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, Hubei University of Science and Technology, Xianning 437100, Hubei, People's Republic of China
| | - Mengxi Li
- School of Nuclear Technology and Chemistry & Biology, Hubei University of Science and Technology, Xianning 437100, Hubei, People's Republic of China
| | - Zhenwang Zhang
- Hubei provincial key laboratory of diabetic cardiovascular diseases, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, Hubei, People's Republic of China
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Feucht D, Kerscher SR, Ruff C, Schuhmann MU, Roder C, Zipfel J. Retrospective longitudinal assessment of optic nerve sheath diameter in patients with malignant glioma. Cancer Med 2023; 12:22047-22055. [PMID: 38063340 PMCID: PMC10757086 DOI: 10.1002/cam4.6789] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2023] [Revised: 09/25/2023] [Accepted: 11/23/2023] [Indexed: 12/31/2023] Open
Abstract
INTRODUCTION Glioblastoma (GBM) is a tumor with rapid growth and a possible relationship to elevated intracranial pressure (ICP). High ICP may not always be associated with clinical signs. A non-invasive technique for assessment of ICP is measuring the optic nerve sheath diameter (ONSD). Identifying patients who need immediate intervention is of importance in neuro-oncological care. The goal of this study is to assess the available magnetic resonance imaging (MRI) of patients with GBM with respect to pre- and postoperative ONSD. METHODS AND MATERIALS Retrospective data analysis was performed on all patients operated for GBM at a tertiary care center between 2010 and 2020. Two pre and one postoperative MRI had to be available. Clinical data and ONSD at multiple time points were analyzed and correlated, as well as preoperative volumetrics. RESULTS Sixty-seven patients met the inclusion criteria. Clinical signs of elevated ICP were seen in 25.4% (n = 17), while significant perifocal edema was present in 67.2% (n = 45) of patients. Clinical signs of preoperatively elevated ICP were associated with significantly elevated ONSD at diagnosis (p < 0.001) as well as preoperative tumor volume (p < 0.001). Significant perifocal edema at the time of diagnosis was associated with elevated ONSD (p = 0.029) and higher tumor volume (p = 0.003). In patients with significant edema, ONSD increased significantly between preoperative MRIs (p = 0.003/005). In patients with clinical signs of raised ICP, ONSD also increased, whereas it was stable in asymptomatic patients (yes: 5.01+/-4.17 to 5.83+/-0.55 mm, p = 0.010, no: 5.17+/-0.46 mm to 5.38+/-0.41 mm, p = 0.81). A significant increase of ONSD from diagnosis to preoperative MRI and a significant decrease until 3 months postoperatively were observed (p < 0.001). CONCLUSIONS ONSD might help identify high ICP in patients with GBM. In this first-of-its kind study, we observed a significant increase of ONSD preoperatively, likely associated with edema. Postoperatively, ONSD decreased significantly until 3 months after surgery and increased again at 12 months. Further prospective data collection is warranted.
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Affiliation(s)
- Daniel Feucht
- Department of NeurosurgeryUniversity Hospital of TuebingenTubingenGermany
| | - Susanne R. Kerscher
- Department of Diagnostic and Interventional RadiologyUniversity Hospital of UlmUlmGermany
| | - Christer Ruff
- Department of Diagnostic and Interventional NeuroradiologyUniversity Hospital of TuebingenTubingenGermany
| | | | - Constantin Roder
- Department of NeurosurgeryUniversity Hospital of TuebingenTubingenGermany
| | - Julian Zipfel
- Department of NeurosurgeryUniversity Hospital of TuebingenTubingenGermany
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Indriani RV, Munir G, Dewayani BM. A rare case of multiple supratentorial brain lesions due to meningiomatosis. Radiol Case Rep 2023; 18:3997-4001. [PMID: 37691764 PMCID: PMC10491766 DOI: 10.1016/j.radcr.2023.08.037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Accepted: 08/04/2023] [Indexed: 09/12/2023] Open
Abstract
Meningeal tumors represent the most common primary central nervous system tumors. The term "multiple meningiomas" or "meningiomatosis" refers to the occurrence of 2 or more spatially separated meningiomas without the features of neurofibromatosis. Meningiomatosis accounts for only less than 10% of all cases and is more prevalent in women. We report a rare case of a 53-year-old female patient complaining of a headache characterized by a throbbing pain in the right side of the head. Neurological examination was largely normal, with the exception of a slight weakening of the right extremity. Multiple brain masses, due to meningiomatosis, were revealed upon CT scan and MRI. Subsequent tissue biopsy confirmed the diagnosis of meningothelial meningiomas.
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Affiliation(s)
- R. Vera Indriani
- Department of Radiology, Faculty of Medicine, Hasan Sadikin General Hospital, Padjadjaran University, Jl. Pasteur No.38, Pasteur, Bandung, West Java, 40161 Indonesia
| | - Gustiara Munir
- Department of Radiology, Faculty of Medicine, Hasan Sadikin General Hospital, Padjadjaran University, Jl. Pasteur No.38, Pasteur, Bandung, West Java, 40161 Indonesia
| | - Birgitta M. Dewayani
- Department of Pathology Anatomy, Faculty of Medicine, Hasan Sadikin General Hospital, Padjadjaran University, Jl. Pasteur No.38, Pasteur, Bandung, West Java, 40161 Indonesia
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Pontes B, Mendes FA. Mechanical Properties of Glioblastoma: Perspectives for YAP/TAZ Signaling Pathway and Beyond. Diseases 2023; 11:86. [PMID: 37366874 DOI: 10.3390/diseases11020086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 06/06/2023] [Accepted: 06/12/2023] [Indexed: 06/28/2023] Open
Abstract
Glioblastoma is a highly aggressive brain tumor with a poor prognosis. Recent studies have suggested that mechanobiology, the study of how physical forces influence cellular behavior, plays an important role in glioblastoma progression. Several signaling pathways, molecules, and effectors, such as focal adhesions, stretch-activated ion channels, or membrane tension variations, have been studied in this regard. Also investigated are YAP/TAZ, downstream effectors of the Hippo pathway, which is a key regulator of cell proliferation and differentiation. In glioblastoma, YAP/TAZ have been shown to promote tumor growth and invasion by regulating genes involved in cell adhesion, migration, and extracellular matrix remodeling. YAP/TAZ can be activated by mechanical cues such as cell stiffness, matrix rigidity, and cell shape changes, which are all altered in the tumor microenvironment. Furthermore, YAP/TAZ have been shown to crosstalk with other signaling pathways, such as AKT, mTOR, and WNT, which are dysregulated in glioblastoma. Thus, understanding the role of mechanobiology and YAP/TAZ in glioblastoma progression could provide new insights into the development of novel therapeutic strategies. Targeting YAP/TAZ and mechanotransduction pathways in glioblastoma may offer a promising approach to treating this deadly disease.
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Affiliation(s)
- Bruno Pontes
- Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil
- Centro Nacional de Biologia Estrutural e Bioimagem (CENABIO), Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil
| | - Fabio A Mendes
- Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil
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Adegbesan KA, Tomassoni Ardori F, Yanpallewar S, Bradley SP, Chudasama Y, Vera E, Briceno N, King AL, Tessarollo L, Gilbert MR, Guedes VA, Smart DK, Armstrong TS, Shuboni-Mulligan DD. The sex-dependent impact of PER2 polymorphism on sleep and activity in a novel mouse model of cranial-irradiation-induced hypersomnolence. Neurooncol Adv 2023; 5:vdad108. [PMID: 37781088 PMCID: PMC10540885 DOI: 10.1093/noajnl/vdad108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/03/2023] Open
Abstract
Background Hypersomnolence is a common and disruptive side effect of cranial radiotherapy and is associated with fatigue and disturbances in mood and cognition in primary brain tumor (PBT) patients. The biological underpinnings of this effect are not understood. Our laboratory has previously found that the presence of a single nucleotide polymorphism (rs934945, G-E mutation) in the PERIOD2 (PER2) clock gene was associated with a decreased likelihood of fatigue in PBT patients. Here, we aim to understand the effects of PER2 polymorphism on radiation susceptibility within a murine model of cranial-irradiation-induced hypersomnolence (C-RIH). Methods Male and female transgenic mice were generated using CRISPR-Cas9, replacing the endogenous mouse PER2:CRY1 binding domain with its human isoform with (hE1244 KI) or without the SNP rs934945 (hG1244 KI). Activity and sleep were monitored continuously 10 days before and after cranial irradiation (whole brain, 15Gy, single fraction). Behavioral assessments measuring anxiety, depression, and working memory were used to assess mood and cognitive changes 2 months postradiation. Results During their active phase, hE1244 knock-ins (KIs) had less radiation-induced suppression of activity relative to hG1244 KIs and female hE1244 KIs saw a reduction of hypersomnolence over 10 days. hE1244 KIs displayed less anxiety behavior and were more ambulatory within all behavioral tests. Conclusions The PER2 rs934945 polymorphism had long-lasting behavioral effects associated with radiation toxicity, particularly in sleep in females and the activity of all animals. Our findings shed light on biological mechanisms underlying C-RIH.
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Affiliation(s)
- Kendra A Adegbesan
- Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Francesco Tomassoni Ardori
- Neural Development Section, Mouse Cancer Genetics Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Sudhirkumar Yanpallewar
- Neural Development Section, Mouse Cancer Genetics Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Sean P Bradley
- Rodent Behavior Core, National Institute of Mental Health, National Institutes of Health, Frederick, MD, USA
| | - Yogita Chudasama
- Rodent Behavior Core, National Institute of Mental Health, National Institutes of Health, Frederick, MD, USA
- Section on Behavioral Neuroscience, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
| | - Elizabeth Vera
- Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Nicole Briceno
- Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Amanda L King
- Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Lino Tessarollo
- Neural Development Section, Mouse Cancer Genetics Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Mark R Gilbert
- Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Vivian A Guedes
- Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - DeeDee K Smart
- Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Terri S Armstrong
- Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
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McCullagh K, Castillo M, Zamora C. Headache Attributed to Non-vascular Intracranial Disorder: Neoplasms, Infections, and Substance Abuse. Neurol Clin 2022; 40:531-546. [PMID: 35871783 DOI: 10.1016/j.ncl.2022.02.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
Evaluation of headaches warrants a careful history and neurologic assessment to determine the need for further workup and imaging. Identifying patients who are at risk for underlying pathology is important and this includes individuals with known or suspected malignancy and those who are immunocompromised and at increased risk for intracranial infection. While CT is helpful in the acute setting and to screen for intracranial hypertension, MRI is the modality of choice for the evaluation of underlying pathologies. Imaging in substance abuse may show injury related to direct toxicity or secondary to vascular complications.
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Affiliation(s)
- Kassie McCullagh
- Division of Neuroradiology, Department of Radiology, The University of North Carolina at Chapel Hill, CB 7510 2000 Old Clinic, 101 Manning Drive, Chapel Hill, NC 27599, USA.
| | - Mauricio Castillo
- Division of Neuroradiology, Department of Radiology, The University of North Carolina at Chapel Hill, CB 7510 2000 Old Clinic, 101 Manning Drive, Chapel Hill, NC 27599, USA
| | - Carlos Zamora
- Division of Neuroradiology, Department of Radiology, The University of North Carolina at Chapel Hill, CB 7510 2000 Old Clinic, 101 Manning Drive, Chapel Hill, NC 27599, USA
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13
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Khoonkari M, Liang D, Kamperman M, Kruyt FAE, van Rijn P. Physics of Brain Cancer: Multiscale Alterations of Glioblastoma Cells under Extracellular Matrix Stiffening. Pharmaceutics 2022; 14:pharmaceutics14051031. [PMID: 35631616 PMCID: PMC9145282 DOI: 10.3390/pharmaceutics14051031] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 04/27/2022] [Accepted: 05/06/2022] [Indexed: 12/12/2022] Open
Abstract
The biology and physics underlying glioblastoma is not yet completely understood, resulting in the limited efficacy of current clinical therapy. Recent studies have indicated the importance of mechanical stress on the development and malignancy of cancer. Various types of mechanical stress activate adaptive tumor cell responses that include alterations in the extracellular matrix (ECM) which have an impact on tumor malignancy. In this review, we describe and discuss the current knowledge of the effects of ECM alterations and mechanical stress on GBM aggressiveness. Gradual changes in the brain ECM have been connected to the biological and physical alterations of GBM cells. For example, increased expression of several ECM components such as glycosaminoglycans (GAGs), hyaluronic acid (HA), proteoglycans and fibrous proteins result in stiffening of the brain ECM, which alters inter- and intracellular signaling activity. Several mechanosensing signaling pathways have been identified that orchestrate adaptive responses, such as Hippo/YAP, CD44, and actin skeleton signaling, which remodel the cytoskeleton and affect cellular properties such as cell–cell/ECM interactions, growth, and migration/invasion of GBM cells. In vitro, hydrogels are used as a model to mimic the stiffening of the brain ECM and reconstruct its mechanics, which we also discuss. Overall, we provide an overview of the tumor microenvironmental landscape of GBM with a focus on ECM stiffening and its associated adaptive cellular signaling pathways and their possible therapeutic exploitation.
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Affiliation(s)
- Mohammad Khoonkari
- Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; (M.K.); (D.L.)
- Polymer Science, Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands;
| | - Dong Liang
- Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; (M.K.); (D.L.)
| | - Marleen Kamperman
- Polymer Science, Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands;
| | - Frank A. E. Kruyt
- Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; (M.K.); (D.L.)
- Correspondence: (F.A.E.K.); (P.v.R.)
| | - Patrick van Rijn
- Department of Biomedical Engineering-FB40, University of Groningen, University Medical Center Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands
- W.J. Kolff Institute for Biomedical Engineering and Materials Science-FB41, University of Groningen, University Medical Center Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands
- Correspondence: (F.A.E.K.); (P.v.R.)
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14
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Hemodynamic Imaging in Cerebral Diffuse Glioma-Part A: Concept, Differential Diagnosis and Tumor Grading. Cancers (Basel) 2022; 14:cancers14061432. [PMID: 35326580 PMCID: PMC8946242 DOI: 10.3390/cancers14061432] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Revised: 03/01/2022] [Accepted: 03/08/2022] [Indexed: 11/17/2022] Open
Abstract
Diffuse gliomas are the most common primary malignant intracranial neoplasms. Aside from the challenges pertaining to their treatment-glioblastomas, in particular, have a dismal prognosis and are currently incurable-their pre-operative assessment using standard neuroimaging has several drawbacks, including broad differentials diagnosis, imprecise characterization of tumor subtype and definition of its infiltration in the surrounding brain parenchyma for accurate resection planning. As the pathophysiological alterations of tumor tissue are tightly linked to an aberrant vascularization, advanced hemodynamic imaging, in addition to other innovative approaches, has attracted considerable interest as a means to improve diffuse glioma characterization. In the present part A of our two-review series, the fundamental concepts, techniques and parameters of hemodynamic imaging are discussed in conjunction with their potential role in the differential diagnosis and grading of diffuse gliomas. In particular, recent evidence on dynamic susceptibility contrast, dynamic contrast-enhanced and arterial spin labeling magnetic resonance imaging are reviewed together with perfusion-computed tomography. While these techniques have provided encouraging results in terms of their sensitivity and specificity, the limitations deriving from a lack of standardized acquisition and processing have prevented their widespread clinical adoption, with current efforts aimed at overcoming the existing barriers.
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15
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Khan A, Azadian M, Richter D, Young TP, Kuntz HM. Clinical Presentation of Toddlers With New Intracranial Space-Occupying Lesions: A Case Series. Pediatr Emerg Care 2022; 38:e618-e621. [PMID: 33760576 DOI: 10.1097/pec.0000000000002388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
OBJECTIVE Intracranial space occupying lesions (ICSOLs) like tumors and abscesses can be life-threatening conditions. It can be especially difficult to diagnose these conditions in toddlers. We aimed to describe symptoms and signs present in a sample of toddlers with ICSOLs. METHODS We performed a retrospective chart review of 15 toddlers with intracranial tumors, abscesses, or infected cysts. We collected data on the presence of various signs and symptoms on presentation to the emergency department. RESULTS Eight toddlers (53%) presented with vomiting. A change in behavior was the second most common symptom (6, 40%). Seven children (47%) had motor weakness, and 5 (33%) had ataxia. Eleven of the 12 children with tumors (92%) had documented abnormal neurologic signs on initial physical examination. CONCLUSIONS Vomiting, a change in behavior, and an abnormal neurologic examination were common signs and symptoms in our sample of toddlers with ICSOLs. An accurate history and appropriate neurologic examination can help physicians make this challenging diagnosis in this age group.
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Affiliation(s)
- Abdullah Khan
- From the Department of Emergency Medicine, Pediatric Emergency Medicine, Loma Linda University Hospital, Loma Linda, CA
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16
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Griffin CP, Paul CL, Alexander KL, Walker MM, Hondermarck H, Lynam J. Postmortem brain donations vs premortem surgical resections for glioblastoma research: viewing the matter as a whole. Neurooncol Adv 2022; 4:vdab168. [PMID: 35047819 PMCID: PMC8760897 DOI: 10.1093/noajnl/vdab168] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
There have been limited improvements in diagnosis, treatment, and outcomes of primary brain cancers, including glioblastoma, over the past 10 years. This is largely attributable to persistent deficits in understanding brain tumor biology and pathogenesis due to a lack of high-quality biological research specimens. Traditional, premortem, surgical biopsy samples do not allow full characterization of the spatial and temporal heterogeneity of glioblastoma, nor capture end-stage disease to allow full evaluation of the evolutionary and mutational processes that lead to treatment resistance and recurrence. Furthermore, the necessity of ensuring sufficient viable tissue is available for histopathological diagnosis, while minimizing surgically induced functional deficit, leaves minimal tissue for research purposes and results in formalin fixation of most surgical specimens. Postmortem brain donation programs are rapidly gaining support due to their unique ability to address the limitations associated with surgical tissue sampling. Collecting, processing, and preserving tissue samples intended solely for research provides both a spatial and temporal view of tumor heterogeneity as well as the opportunity to fully characterize end-stage disease from histological and molecular standpoints. This review explores the limitations of traditional sample collection and the opportunities afforded by postmortem brain donations for future neurobiological cancer research.
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Affiliation(s)
- Cassandra P Griffin
- School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia
- Hunter Cancer Biobank: NSW Regional Biospecimen and Research Services, University of Newcastle, Callaghan, New South Wales, Australia
- Hunter Cancer Research Alliance, University of Newcastle, Newcastle, New South Wales, Australia
- Hunter Medical Research Institute, Newcastle, New South Wales, Australia
| | - Christine L Paul
- School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia
- Hunter Cancer Research Alliance, University of Newcastle, Newcastle, New South Wales, Australia
- Hunter Medical Research Institute, Newcastle, New South Wales, Australia
- Priority Research Centre Cancer Research, Innovation and Translation, University of Newcastle, New South Wales, Australia
- Priority Research Centre Health Behaviour, University of Newcastle, New South Wales, Australia
| | - Kimberley L Alexander
- Neurosurgery Department, Chris O’Brien Lifehouse, Camperdown, New South Wales, Australia
- Brainstorm Brain Cancer Research, Brain and Mind Centre, The University of Sydney, New South Wales, Australia
- Neuropathology Department, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
| | - Marjorie M Walker
- School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia
- Hunter Cancer Research Alliance, University of Newcastle, Newcastle, New South Wales, Australia
- Hunter Medical Research Institute, Newcastle, New South Wales, Australia
| | - Hubert Hondermarck
- Hunter Cancer Research Alliance, University of Newcastle, Newcastle, New South Wales, Australia
- Hunter Medical Research Institute, Newcastle, New South Wales, Australia
- School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia
| | - James Lynam
- School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia
- Hunter Cancer Research Alliance, University of Newcastle, Newcastle, New South Wales, Australia
- Department of Medical Oncology, Calvary Mater, Newcastle, New South Wales, Australia
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17
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Wei JH, Tian YN, Zhang YZ, Wang XJ, Guo H, Mao JH. Short-term effect and long-term prognosis of neuroendoscopic minimally invasive surgery for hypertensive int racerebral hemorrhage. World J Clin Cases 2021;9:8358-8365. [PMID: 34754845 PMCID: PMC8554417 DOI: 10.12998/wjcc.v9.i28.8358] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Revised: 07/02/2021] [Accepted: 08/05/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hypertensive intracerebral hemorrhage is a common critical disease of the nervous system, comprising one fifth of all acute cerebrovascular diseases and has a high disability and mortality rate. It severely affects the patients’ quality of life.
AIM To analyze the short-term effect and long-term prognosis of neuroendoscopic minimally invasive surgery for hypertensive intracerebral hemorrhage.
METHODS From March 2018 to May 2020, 118 patients with hypertensive intracerebral hemorrhage were enrolled in our study and divided into a control group and observation group according to the surgical plan. The control group used a hard-channel minimally invasive puncture and drainage procedure. The observation group underwent minimally invasive neuroendoscopic surgery. The changes in the levels of serum P substances (SP), inflammatory factors [tumor necrosis factor-α, interleukin-6 (IL-6), IL-10], and the National Hospital Stroke Scale (NIHSS) and Barthel index scores were recorded. Surgery related indicators and prognosis were compared between the two groups.
RESULTS The operation time (105.26 ± 28.35) of the observation group was min longer than that of the control group, and the volume of intraoperative bleeding was 45.36 ± 10.17 mL more than that of the control group. The hematoma clearance rates were 88.58% ± 4.69% and 94.47% ± 4.02% higher than those of the control group at 48 h and 72 h, respectively. Good prognosis rate (86.44%) was higher in the observation group than in the control group, and complication rate (5.08%) was not significantly different from that of the control group (P > 0.05).The SP level and Barthel index score of the two groups increased (P < 0.05) and the inflammatory factors and NIHSS score decreased (P < 0.05). The cytokine levels, NIHSS score, and Barthel index score were better in the observation group than in the control group (P < 0.05).
CONCLUSION Neuroendoscopic minimally invasive surgery is more complicated than hard channel minimally invasive puncture drainage in the treatment of hypertensive intracerebral hemorrhage; however, hematoma clearance is more thorough, and the short-term effect and long-term prognosis are better than hard channel minimally invasive puncture drainage.
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Affiliation(s)
- Jian-Hui Wei
- Department of Neurosurgery, Harrison International Peace Hospital, Hengshui 053000, Hebei Province, China
| | - Ya-Nan Tian
- Department of Neurology, Harrison International Peace Hospital, Hengshui 053000, Hebei Province, China
| | - Ya-Zhao Zhang
- Department of Neurology, Harrison International Peace Hospital, Hengshui 053000, Hebei Province, China
| | - Xue-Jing Wang
- Department of Neurology, Harrison International Peace Hospital, Hengshui 053000, Hebei Province, China
| | - Hong Guo
- Department of Neurology, Harrison International Peace Hospital, Hengshui 053000, Hebei Province, China
| | - Jian-Hui Mao
- Department of Neurology, Harrison International Peace Hospital, Hengshui 053000, Hebei Province, China
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18
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Increased Intracranial Pressure: The Use of an Individualized Ladder Approach. Semin Oncol Nurs 2021; 37:151133. [PMID: 33663885 DOI: 10.1016/j.soncn.2021.151133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
OBJECTIVE This paper provides a review of current knowledge on intracranial pressure (ICP) dynamics, assessment, and diagnostic considerations, and presents a ladder approach to the management of the neuro-oncological emergency increased ICP. DATA SOURCE Review of recent literature from PubMed. CONCLUSION Increased ICP can rapidly escalate into a catastrophic event. Prompt initiation of an individualized ladder approach to clinical management enabled by early recognition of symptoms and application of diagnostic tools have been shown to improve outcomes in patients suffering from this neuro-oncological emergency. IMPLICATIONS FOR NURSING PRACTICE The care of cancer patients with increased ICP can be very challenging. When increased ICP in patients with cancer is evident or strongly suspected, nurses need to initiate a prompt and effective care plan that includes intensive monitoring of symptoms and continuous assessment of the patient's neurological condition that will guide diagnostic and treatment decisions. Nurses must continue to recognize the importance of utilizing best available evidence to support a collaborative interdisciplinary clinical plan of care.
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19
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Sorribes IC, Handelman SK, Jain HV. Mitigating temozolomide resistance in glioblastoma via DNA damage-repair inhibition. J R Soc Interface 2020; 17:20190722. [PMID: 31964274 DOI: 10.1098/rsif.2019.0722] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Glioblastomas are among the most lethal cancers, with a 5 year survival rate below 25%. Temozolomide is typically used in glioblastoma treatment; however, the enzymes alkylpurine-DNA-N-glycosylase (APNG) and methylguanine-DNA-methyltransferase (MGMT) efficiently mediate the repair of DNA damage caused by temozolomide, reducing treatment efficacy. Consequently, APNG and MGMT inhibition has been proposed as a way of overcoming chemotherapy resistance. Here, we develop a mechanistic mathematical model that explicitly incorporates the effects of chemotherapy on tumour cells, including the processes of DNA damage induction, cell arrest and DNA repair. Our model is carefully parametrized and validated, and then used to virtually recreate the response of heteroclonal glioblastomas to dual treatment with temozolomide and inhibitors of APNG/MGMT. Using our mechanistic model, we identify four combination treatment strategies optimized by tumour cell phenotype, and isolate the strategy most likely to succeed in a pre-clinical and clinical setting. If confirmed in clinical trials, these strategies have the potential to offset chemotherapy resistance in patients with glioblastoma and improve overall survival.
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Affiliation(s)
| | - Samuel K Handelman
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
| | - Harsh V Jain
- Department of Mathematics, Florida State University, Tallahassee, FL 32306, USA
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