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Journal of Neuro-oncology Sep 2023Despite aggressive management consisting of surgery, radiation therapy (RT), and systemic therapy given alone or in combination, a significant proportion of patients... (Review)
Review
Despite aggressive management consisting of surgery, radiation therapy (RT), and systemic therapy given alone or in combination, a significant proportion of patients with brain tumors will experience tumor recurrence. For these patients, no standard of care exists and management of either primary or metastatic recurrent tumors remains challenging.Advances in imaging and RT technology have enabled more precise tumor localization and dose delivery, leading to a reduction in the volume of health brain tissue exposed to high radiation doses. Radiation techniques have evolved from three-dimensional (3-D) conformal RT to the development of sophisticated techniques, including intensity modulated radiation therapy (IMRT), volumetric arc therapy (VMAT), and stereotactic techniques, either stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT). Several studies have suggested that a second course of RT is a feasible treatment option in patients with a recurrent tumor; however, survival benefit and treatment related toxicity of reirradiation, given alone or in combination with other focal or systemic therapies, remain a controversial issue.We provide a critical overview of the current clinical status and technical challenges of reirradiation in patients with both recurrent primary brain tumors, such as gliomas, ependymomas, medulloblastomas, and meningiomas, and brain metastases. Relevant clinical questions such as the appropriate radiation technique and patient selection, the optimal radiation dose and fractionation, tolerance of the brain to a second course of RT, and the risk of adverse radiation effects have been critically discussed.
Topics: Humans; Re-Irradiation; Neoplasm Recurrence, Local; Brain Neoplasms; Radiotherapy, Conformal; Radiosurgery; Cerebellar Neoplasms
PubMed: 37624529
DOI: 10.1007/s11060-023-04407-2 -
Cell Reports Oct 2023Esophageal squamous-cell carcinoma (ESCC) is commonly treated with radiotherapy; however, radioresistance hinders its clinical effectiveness, and the underlying...
Esophageal squamous-cell carcinoma (ESCC) is commonly treated with radiotherapy; however, radioresistance hinders its clinical effectiveness, and the underlying mechanism remains elusive. Here, we develop patient-derived xenografts (PDXs) from 19 patients with ESCC to investigate the mechanisms driving radioresistance. Using RNA sequencing, cytokine arrays, and single-cell RNA sequencing, we reveal an enrichment of cancer-associated fibroblast (CAF)-derived collagen type 1 (Col1) and tumor-cell-derived CXCL1 in non-responsive PDXs. Col1 not only promotes radioresistance by augmenting DNA repair capacity but also induces CXCL1 secretion in tumor cells. Additionally, CXCL1 further activates CAFs via the CXCR2-STAT3 pathway, establishing a positive feedback loop. Directly interfering with tumor-cell-derived CXCL1 or inhibiting the CXCL1-CXCR2 pathway effectively restores the radiosensitivity of radioresistant xenografts in vivo. Collectively, our study provides a comprehensive understanding of the molecular mechanisms underlying radioresistance and identifies potential targets to improve the efficacy of radiotherapy for ESCC.
Topics: Humans; Cancer-Associated Fibroblasts; Carcinoma, Squamous Cell; Cell Line, Tumor; Chemokine CXCL1; Collagen; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Radiation Tolerance
PubMed: 37851572
DOI: 10.1016/j.celrep.2023.113270 -
Food & Function Jul 2023High-fat diet (HFD) increases the risk of developing malignant tumors. Ionizing radiation (IR) is used as an adjuvant treatment in oncology. In this study, we...
High-fat diet (HFD) increases the risk of developing malignant tumors. Ionizing radiation (IR) is used as an adjuvant treatment in oncology. In this study, we investigated the effects of an 8-week 35% fat HFD on the tolerance to IR and the modulatory effect of melatonin (MLT). The results of lethal dose irradiation survival experiments revealed that the 8-week HFD altered the radiation tolerance of female mice and increased their radiosensitivity, whereas it had no comparable effects on males. Pre-treatment with MLT was, however, found to attenuate the radiation-induced hematopoietic damage in mice, promote intestinal structural repair after whole abdominal irradiation (WAI), and enhance the regeneration of Lgr5 intestinal stem cells. 16S rRNA high-throughput sequencing and untargeted metabolome analyses revealed that HFD consumption and WAI sex-specifically altered the composition of intestinal microbiota and fecal metabolites and that MLT supplementation differentially modulated the composition of the intestinal microflora in mice. However, in both males and females, different bacteria were associated with the modulation of the metabolite 5-methoxytryptamine. Collectively, the findings indicate that MLT ameliorates the radiation-induced damage and sex-specifically shapes the composition of the gut microbiota and metabolites, protecting mice from the adverse side effects associated with HFD and IR.
Topics: Male; Mice; Female; Animals; Melatonin; Diet, High-Fat; RNA, Ribosomal, 16S; Intestines; Radiation Tolerance; Mice, Inbred C57BL
PubMed: 37401725
DOI: 10.1039/d3fo01831h -
Radiotherapy and Oncology : Journal of... Dec 2023Radiotherapy is a widely used treatment modality against cancer, and although survival rates are increasing, radioresistant properties of tumours remain a significant... (Review)
Review
Radiotherapy is a widely used treatment modality against cancer, and although survival rates are increasing, radioresistant properties of tumours remain a significant barrier for curative treatment. Tumour hypoxia is one of the main contributors to radioresistance and is common in most solid tumours. Hypoxia is responsible for many molecular changes within the cell which helps tumours to survive under such challenging conditions. These hypoxia-induced molecular changes are predominantly coordinated by the hypoxia inducible factor (HIF) and have been linked with the ability to confer resistance to radiation-induced cell death. To overcome this obstacle research has been directed towards autophagy, a cellular process involved in self degradation and recycling of macromolecules, as HIF plays a large role in its coordination under hypoxic conditions. The role that autophagy has following radiotherapy treatment is conflicted with evidence of both cytoprotective and cytotoxic effects. This literature review aims to explore the intricate relationship between radiotherapy, hypoxia, and autophagy in the context of cancer treatment. It provides valuable insights into the potential of targeting autophagy as a therapeutic strategy to improve the response of hypoxic tumours to radiotherapy.
Topics: Humans; Radiation Tolerance; Neoplasms; Hypoxia; Cell Hypoxia; Autophagy; Cell Line, Tumor; Hypoxia-Inducible Factor 1, alpha Subunit
PubMed: 37838322
DOI: 10.1016/j.radonc.2023.109951 -
Laryngo- Rhino- Otologie Sep 2023
Topics: Humans; Laryngeal Neoplasms; Larynx; Radiation Tolerance
PubMed: 37657431
DOI: 10.1055/a-2093-2445 -
Nature Communications Aug 2023Radiation tolerance is determined as the ability of crystalline materials to withstand the accumulation of the radiation induced disorder. Nevertheless, for sufficiently...
Radiation tolerance is determined as the ability of crystalline materials to withstand the accumulation of the radiation induced disorder. Nevertheless, for sufficiently high fluences, in all by far known semiconductors it ends up with either very high disorder levels or amorphization. Here we show that gamma/beta (γ/β) double polymorph GaO structures exhibit remarkably high radiation tolerance. Specifically, for room temperature experiments, they tolerate a disorder equivalent to hundreds of displacements per atom, without severe degradations of crystallinity; in comparison with, e.g., Si amorphizable already with the lattice atoms displaced just once. We explain this behavior by an interesting combination of the Ga- and O- sublattice properties in γ-GaO. In particular, O-sublattice exhibits a strong recrystallization trend to recover the face-centered-cubic stacking despite the stronger displacement of O atoms compared to Ga during the active periods of cascades. Notably, we also explained the origin of the β-to-γ GaO transformation, as a function of the increased disorder in β-GaO and studied the phenomena as a function of the chemical nature of the implanted atoms. As a result, we conclude that γ/β double polymorph GaO structures, in terms of their radiation tolerance properties, benchmark a class of universal radiation tolerant semiconductors.
PubMed: 37563159
DOI: 10.1038/s41467-023-40588-0 -
Clinical and Translational Medicine Sep 2023Super enhancers (SE) play pivotal roles in cell identity and diseases occur including tumorigenesis. The depletion of SE-associated lncRNA transcripts, also known as...
METTL3-stabilized super enhancers-lncRNA SUCLG2-AS1 mediates the formation of a long-range chromatin loop between enhancers and promoters of SOX2 in metastasis and radiosensitivity of nasopharyngeal carcinoma.
BACKGROUND
Super enhancers (SE) play pivotal roles in cell identity and diseases occur including tumorigenesis. The depletion of SE-associated lncRNA transcripts, also known as super-lncRNA, causes the activity of SE to be dysregulated.
METHODS
We screened and identified an elevated metastasis-associated SE-lncRNA SUCLG2-AS1 in nasopharyngeal carcinoma (NPC) using RNA-sequencing, real-time quantitative polymerase chain reaction (RT-qPCR) and bioinformatics. Western blotting, RT-qPCR, methylated RNA immunoprecipitation (MeRIP), RNA immunoprecipitation, chromatin immunoprecipitation, RNA pull-down and 3C (chromosome conformation capture assays) were used for mechanistic studies.
RESULTS
SUCLG2-AS1 was correlated with a poor prognosis. SUCLG2-AS1 promotes NPC cell invasion and metastasis while repressing apoptosis and radiosensitivity in vitro and in vivo. Mechanistically, high SUCLG2-AS1 expression occurred in an m6A-dependent manner. SUCLG2-AS1 was found to be located in the SE region of SOX2, and it regulated the expression of SOX2 via long-range chromatin loop formation, which via mediating CTCF (transcription factor) occupied the SE and promoter region of SOX2, thus regulating the metastasis and radiosensitivity of NPC.
CONCLUSIONS
Taken together, our data suggest that SUCLG2-AS1 may serve as a novel intervention target for the clinical treatment of NPC.
Topics: Humans; Chromatin; RNA, Long Noncoding; Nasopharyngeal Carcinoma; Promoter Regions, Genetic; Radiation Tolerance; Chromatin Immunoprecipitation; Nasopharyngeal Neoplasms; Methyltransferases; SOXB1 Transcription Factors
PubMed: 37658588
DOI: 10.1002/ctm2.1361 -
ArXiv Oct 2023The genetic basis of phenotypic differences between species is among the most longstanding questions in evolutionary biology. How new genes form and the processes...
The genetic basis of phenotypic differences between species is among the most longstanding questions in evolutionary biology. How new genes form and the processes selection acts to produce differences across species are fundamental to understand how species persist and evolve in an ever-changing environment. Adaptation and genetic innovation arise in the genome by a variety of sources. Functional genomics requires both intrinsic genetic discoveries, as well as empirical testing to observe adaptation between lineages. Here we explore two species of Drosophila on the island of Sao Tome and mainland Africa, D. santomea and D. yakuba. These two species both inhabit the island, but occupy differing species distributions based on elevation, with D. yakuba also having populations on mainland Africa. Intrinsic evidence shows genes between species may have a role in adaptation to higher UV tolerance with DNA repair mechanisms (PARP) and resistance to humeral stress lethal effects (Victoria). We conducted empirical assays between island D. santomea, D. yakuba, and mainland D. yakuba. Flies were shocked with UVB radiation (@ 302 nm) at 1650-1990 mW/cm2 for 30 minutes on a transilluminator apparatus. Custom 5-wall acrylic enclosures were constructed for viewing and containment of flies. All assays were filmed. Island groups did show significant differences between fall-time under UV stress and recovery time post-UV stress test between regions and sex. This study shows evidence that mainland flies are less resistant to UV radiation than their island counterparts. Further work exploring the genetic basis for UV tolerance will be conducted from empirical assays. Understanding the mechanisms and processes that promote adaptation and testing extrinsic traits within the context of the genome is crucially important to understand evolutionary machinery.
PubMed: 37873005
DOI: No ID Found -
International Journal of Radiation... Apr 2024Radiation therapy is a primary treatment for cancer, but radioresistance remains a significant challenge in improving efficacy and reducing toxicity. Accumulating... (Review)
Review
Radiation therapy is a primary treatment for cancer, but radioresistance remains a significant challenge in improving efficacy and reducing toxicity. Accumulating evidence suggests that deubiquitinases (DUBs) play a crucial role in regulating cell sensitivity to ionizing radiation. Traditional small-molecule DUB inhibitors have demonstrated radiosensitization effects, and novel deubiquitinase-targeting chimeras (DUBTACs) provide a promising strategy for radiosensitizer development by harnessing the ubiquitin-proteasome system. This review highlights the mechanisms by which DUBs regulate radiosensitivity, including DNA damage repair, the cell cycle, cell death, and hypoxia. Progress on DUB inhibitors and DUBTACs is summarized, and their potential radiosensitization effects are discussed. Developing drugs targeting DUBs appears to be a promising alternative approach to overcoming radioresistance, warranting further research into their mechanisms.
Topics: Humans; Antineoplastic Agents; Proteasome Inhibitors; Neoplasms; Deubiquitinating Enzymes; Radiation Tolerance
PubMed: 38092257
DOI: 10.1016/j.ijrobp.2023.12.003 -
Innovation (Cambridge (Mass.)) Jul 2023The radiation tolerance of energy storage batteries is a crucial index for universe exploration or nuclear rescue work, but there is no thorough investigation of Li...
The radiation tolerance of energy storage batteries is a crucial index for universe exploration or nuclear rescue work, but there is no thorough investigation of Li metal batteries. Here, we systematically explore the energy storage behavior of Li metal batteries under gamma rays. Degradation of the performance of Li metal batteries under gamma radiation is linked to the active materials of the cathode, electrolyte, binder, and electrode interface. Specifically, gamma radiation triggers cation mixing in the cathode active material, which results in poor polarization and capacity. Ionization of solvent molecules in the electrolyte promotes decomposition of LiPF along with its decomposition, and molecule chain breaking and cross-linking weaken the bonding ability of the binder, causing electrode cracking and reduced active material utilization. Additionally, deterioration of the electrode interface accelerates degradation of the Li metal anode and increases cell polarization, hastening the demise of Li metal batteries even more. This work provides significant theoretical and technical evidence for development of Li batteries in radiation environments.
PubMed: 37427353
DOI: 10.1016/j.xinn.2023.100468