Focused Ultrasound-enabled Brain Tumor Liquid Biopsy

Zhu, Lifei; Cheng, Galen; Ye, Dezhuang; Nazeri, Arash; Yue, Yimei; Liu, Wei Jun; Wang, Xiaowei; Dunn, Gavin P.; Petti, Allegra A.; Leuthardt, Eric C.; Chen, Hong

doi:10.1038/s41598-018-24516-7

Cited by 76 publications

(77 citation statements)

References 34 publications

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“…In order to improve this shortcoming, new technologies are needed. For instance, an innovative technique employed focused ultrasound to increase the release of brain tumor material into the bloodstream, essentially making blood a viable surrogate for tumor detection (29).…”

Section: Discussionmentioning

confidence: 99%

TERT Promoter Mutation Detection in Cell-Free Tumor-Derived DNA in Patients with IDH Wild-Type Glioblastomas: A Pilot Prospective Study

Juratli

Stasik

Zolal

et al. 2018

Clinical Cancer Research

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We conducted a pilot study to assess the feasibility and the potential implications of detecting promoter (p)-mutant cell-free tumor-derived DNA (tDNA) in the cerebrospinal fluid (CSF) and plasma of glioblastoma patients. Matched CSF and plasma samples were collected in 60 patients with glial tumors. The CSF collection was obtained during surgery, before any surgical manipulation of the tumor. The extracted tDNA and corresponding tumor DNA samples were analyzed for p and isocitrate dehydrogenase ( hotspot mutations. In addition, the variant allele frequency (VAF) of p mutation in the CSF-tDNA was correlated with tumor features and patients' outcome. Thirty-eight patients had p-mutant/ wild-type glioblastomas. The matched p mutation in the CSF-tDNA was successfully detected with 100% specificity (95% CI, 87.6-100%) and 92.1% sensitivity (95% CI, 78.6-98.3%) ( = 35/38). In contrast, the sensitivity in the plasma-tDNA was far lower [ = 3/38, 7.9% (95% CI, 1.6-21.4%)]. We concordantly observed a longer overall survival of patients with low VAF in the CSF-tDNA when compared with patients with high VAF, irrespective of using the lower quartile VAF [11.45%; 14.0 mo. (95% confidence interval, CI, 10.3-17.6) vs. 8.6 mo. (95% CI, 4.1-13.2), = 0.035], the lower third VAF [13%; 15.4 mo. (95% CI, 11.6-19.2) vs. 8.3 mo. (95% CI, 2.3-14.4), = 0.008], or the median VAF [20.3%; 14.0 mo. (95% CI, 9.2-18.7) vs. 8.6 mo. (95% CI, 7.5-9.8), = 0.062] to dichotomize the patients. This pilot study highlights the value of CSF-tDNA for an accurate and reliable detection of p mutations. Furthermore, our findings suggest that highp mutation VAF levels in the CSF-tDNA may represent a suitable predictor of poor survival in glioblastoma patients. Further studies are needed to complement the findings of our exploratory analysis. .

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Section: Discussionmentioning

confidence: 99%

TERT Promoter Mutation Detection in Cell-Free Tumor-Derived DNA in Patients with IDH Wild-Type Glioblastomas: A Pilot Prospective Study

Juratli

Stasik

Zolal

et al. 2018

Clinical Cancer Research

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“…These biotin-MBs targeted against CD44 receptors efficiently recognized luminal breast cancer cells in PBS, and were able to separate them from the CD44-basal-like breast cancer subset with higher sorting purity than other control MBs [118]. These results contribute to establishing that targeted MBs are an effective new approach to liquid biopsy [119]. As compared to other methods (adherence, absorbance, particle size, density gradient, dielectric properties, chemo-resistance), the antigen-antibody recognition provides precise sorting.…”

Section: Microbubbles In Diagnosis and Ctc Detectionmentioning

confidence: 76%

Nano Meets Micro-Translational Nanotechnology in Medicine: Nano-Based Applications for Early Tumor Detection and Therapy

et al. 2020

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Nanomaterials have great potential for the prevention and treatment of cancer. Circulating tumor cells (CTCs) are cancer cells of solid tumor origin entering the peripheral blood after detachment from a primary tumor. The occurrence and circulation of CTCs are accepted as a prerequisite for the formation of metastases, which is the major cause of cancer-associated deaths. Due to their clinical significance CTCs are intensively discussed to be used as liquid biopsy for early diagnosis and prognosis of cancer. However, there are substantial challenges for the clinical use of CTCs based on their extreme rarity and heterogeneous biology. Therefore, methods for effective isolation and detection of CTCs are urgently needed. With the rapid development of nanotechnology and its wide applications in the biomedical field, researchers have designed various nano-sized systems with the capability of CTCs detection, isolation, and CTCs-targeted cancer therapy. In the present review, we summarize the underlying mechanisms of CTC-associated tumor metastasis, and give detailed information about the unique properties of CTCs that can be harnessed for their effective analytical detection and enrichment. Furthermore, we want to give an overview of representative nano-systems for CTC isolation, and highlight recent achievements in microfluidics and lab-on-a-chip technologies. We also emphasize the recent advances in nano-based CTCs-targeted cancer therapy. We conclude by critically discussing recent CTC-based nano-systems with high therapeutic and diagnostic potential as well as their biocompatibility as a practical example of applied nanotechnology.

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“…This technique, in addition to being noninvasive, allows the selective release of biomarkers from specific areas of the tumor, which may help in understanding the spatial heterogeneity of GBM. [ 120 ]…”

Section: Clinical Management Of Glioblastoma: New Diagnosis Opportunimentioning

confidence: 99%

Advances in the Knowledge of the Molecular Biology of Glioblastoma and Its Impact in Patient Diagnosis, Stratification, and Treatment

2020

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Gliomas are the most common primary brain tumors in adults. They arise in the glial tissue and primarily occur in the brain. Low‐grade tumors of World Health Organization (WHO) grade II tend to progress to high‐grade gliomas of WHO grade III and, eventually, glioblastoma of WHO grade IV, which is the most common and deadly glioma, with a median survival of 12–15 months after final diagnosis. Knowledge of the molecular biology and genetics of glioblastoma has increased significantly in the past few years, giving rise to classification methods that can help in management and stratification of glioblastoma patients. However, glioblastoma remains an incurable disease. Glioblastoma cells have acquired genetic and metabolic adaptations in order to sustain tumor growth and progression, including changes in energetic metabolism, invasive capacity, migration, and angiogenesis, that make it very difficult to find suitable therapeutic targets and to develop effective drugs. The current standard of care for glioblastoma patients is surgery followed by radiotherapy plus concomitant and adjuvant chemotherapy with temozolomide. Although progress in glioblastoma therapies in recent years has been more limited than in other tumors, numerous drugs and targets are being proposed and many clinical trials are underway to develop effective subtype‐specific treatments.

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Focused Ultrasound-enabled Brain Tumor Liquid Biopsy

Cited by 76 publications

References 34 publications

TERT Promoter Mutation Detection in Cell-Free Tumor-Derived DNA in Patients with IDH Wild-Type Glioblastomas: A Pilot Prospective Study

TERT Promoter Mutation Detection in Cell-Free Tumor-Derived DNA in Patients with IDH Wild-Type Glioblastomas: A Pilot Prospective Study

Nano Meets Micro-Translational Nanotechnology in Medicine: Nano-Based Applications for Early Tumor Detection and Therapy

Advances in the Knowledge of the Molecular Biology of Glioblastoma and Its Impact in Patient Diagnosis, Stratification, and Treatment

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