Photonic hyperthermia of malignant peripheral nerve sheath tumors at the third near-infrared biowindow
Abstract
Malignant peripheral nerve sheath tumors (MPNSTs), as typical aggressive sarcomas, typically carry a dismal prognosis. Given the insensitivity of these tumors to traditional chemotherapy and the absence of effective targeted drugs, new therapeutic strategies for efficient MPNSTs treatment are urgently needed. Recently, photothermal therapy (PTT) has demonstrated significant potential in cancer theranostics due to its minimally invasive nature and excellent therapeutic outcomes. However, the passive utilization of photothermal agents (PTAs) with poor target specificity and biocompatibility substantially hinders the clinical translation and application of this method. A unique near-infrared laser at the third biowindow (NIR-III) was utilized for photonic hyperthermia treatment of MPNSTs without PTAs. The superficial locations and relatively high collagen content of MPNSTs ensure the efficiency of photothermal tumor ablation and make the NIR-III laser a suitable therapeutic option that has potential for use in clinical applications. Using human MPNST cell line and xenograft models, it can be found that although the NIR-III photothermal treatment efficiency varied among individuals, which was possibly influenced by different endoplasmic reticulum stress responses (ERSRs), the expected antineoplastic effect was ultimately achieved after adjustment of the power density and radiation duration. The present study provides an intriguing noninvasive therapy for MPNSTs that accelerates the clinical translation of PTT while avoiding the biocompatibility issues arising from PTAs.
Data availability
The generic database-'Dryad' has been chosen.The unique identifier: doi:10.5061/dryad.3bk3j9km7All data generated or analysed during this study are included in the manuscript and supporting file.
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Photonic hyperthermia of malignant peripheral nerve sheath tumors at the third near-infrared biowindowDryad Digital Repository, doi:10.5061/dryad.3bk3j9km7.
Article and author information
Author details
Funding
National Natural Science Foundation of China (82102344)
- Zhichao Wang
National Natural Science Foundation of China (82172228)
- Qingfeng Li
Shanghai Rising star Program (20QA1405600)
- Zhichao Wang
Natural Science Foundation of Shanghai (22ZR1422300)
- Zhichao Wang
Science and Technology Commission of Shanghai Municipality (19JC1413)
- Qingfeng Li
Shanghai Education Development Foundation (19CG18)
- Zhichao Wang
Shanghai Municipal Key Clinical Specialty (shslczdzk00901)
- Qingfeng Li
Innovative research team of high-level local universities in Shanghai (SSMU-ZDCX20180700)
- Qingfeng Li
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Wei Tao, Harvard University, United States
Ethics
Animal experimentation: All animals received humane care in compliance with the guidelines outlined in the Guide for the Care and Use of Laboratory Animals. All procedures were performed in accordance with the guidelines approved by the Shanghai Medical Experimental Animal Care Commission (IACUC: 2019-0008).
Human subjects: The use of photos and magnetic resonance images of MPNST patients was approved by the Ethics Committee of Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine (Reference number: SH9H-2019-T163-2). Informed consent and consent to publish were obtained from patients under institutional review board protocols.
Version history
- Received: November 15, 2021
- Accepted: August 15, 2022
- Accepted Manuscript published: September 16, 2022 (version 1)
- Version of Record published: October 11, 2022 (version 2)
Copyright
© 2022, Gu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Further reading
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- Cancer Biology
- Genetics and Genomics
Enhancers are critical for regulating tissue-specific gene expression, and genetic variants within enhancer regions have been suggested to contribute to various cancer-related processes, including therapeutic resistance. However, the precise mechanisms remain elusive. Using a well-defined drug-gene pair, we identified an enhancer region for dihydropyrimidine dehydrogenase (DPD, DPYD gene) expression that is relevant to the metabolism of the anti-cancer drug 5-fluorouracil (5-FU). Using reporter systems, CRISPR genome-edited cell models, and human liver specimens, we demonstrated in vitro and vivo that genotype status for the common germline variant (rs4294451; 27% global minor allele frequency) located within this novel enhancer controls DPYD transcription and alters resistance to 5-FU. The variant genotype increases recruitment of the transcription factor CEBPB to the enhancer and alters the level of direct interactions between the enhancer and DPYD promoter. Our data provide insight into the regulatory mechanisms controlling sensitivity and resistance to 5-FU.
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- Cancer Biology
- Epidemiology and Global Health
Background:
Age is the most important risk factor for cancer, but aging rates are heterogeneous across individuals. We explored a new measure of aging-Phenotypic Age (PhenoAge)-in the risk prediction of site-specific and overall cancer.
Methods:
Using Cox regression models, we examined the association of Phenotypic Age Acceleration (PhenoAgeAccel) with cancer incidence by genetic risk group among 374,463 participants from the UK Biobank. We generated PhenoAge using chronological age and nine biomarkers, PhenoAgeAccel after subtracting the effect of chronological age by regression residual, and an incidence-weighted overall cancer polygenic risk score (CPRS) based on 20 cancer site-specific polygenic risk scores (PRSs).
Results:
Compared with biologically younger participants, those older had a significantly higher risk of overall cancer, with hazard ratios (HRs) of 1.22 (95% confidence interval, 1.18–1.27) in men, and 1.26 (1.22–1.31) in women, respectively. A joint effect of genetic risk and PhenoAgeAccel was observed on overall cancer risk, with HRs of 2.29 (2.10–2.51) for men and 1.94 (1.78–2.11) for women with high genetic risk and older PhenoAge compared with those with low genetic risk and younger PhenoAge. PhenoAgeAccel was negatively associated with the number of healthy lifestyle factors (Beta = –1.01 in men, p<0.001; Beta = –0.98 in women, p<0.001).
Conclusions:
Within and across genetic risk groups, older PhenoAge was consistently related to an increased risk of incident cancer with adjustment for chronological age and the aging process could be retarded by adherence to a healthy lifestyle.
Funding:
This work was supported by the National Natural Science Foundation of China (82230110, 82125033, 82388102 to GJ; 82273714 to MZ); and the Excellent Youth Foundation of Jiangsu Province (BK20220100 to MZ).