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Frontiers in Immunology 2023As critical executors regulating many cellular operations, proteins determine whether living activities can be performed in an orderly and efficient manner. Precursor... (Review)
Review
As critical executors regulating many cellular operations, proteins determine whether living activities can be performed in an orderly and efficient manner. Precursor proteins are inert and must be modified posttranslationally to enable a wide range of protein types and functions. Protein posttranslational modifications (PTMs) are well recognized as being directly associated with carcinogenesis and immune modulation and have emerged as important targets for cancer detection and treatment. Lactylation (Kla), a novel PTM associated with cellular metabolism found in a wide range of cells, interacts with both histone and nonhistone proteins. Unlike other epigenetic changes, Kla has been linked to poor tumor prognosis in all current studies. Histone Kla can affect gene expression in tumors and immunological cells, thereby promoting malignancy and immunosuppression. Nonhistone proteins can also regulate tumor progression and treatment resistance through Kla. In this review, we aimed to summarize the role of Kla in the onset and progression of cancers, metabolic reprogramming, immunosuppression, and intestinal flora regulation to identify new molecular targets for cancer therapy and provide a new direction for combined targeted therapy and immunotherapy.
Topics: Humans; Histones; Immunosuppression Therapy; Carcinogenesis; Immunotherapy; Epigenesis, Genetic
PubMed: 37646027
DOI: 10.3389/fimmu.2023.1253064 -
Radiology. Imaging Cancer Jul 2023Theranostics is the combination of two approaches-diagnostics and therapeutics-applied for decades in cancer imaging using radiopharmaceuticals or paired... (Review)
Review
Theranostics is the combination of two approaches-diagnostics and therapeutics-applied for decades in cancer imaging using radiopharmaceuticals or paired radiopharmaceuticals to image and selectively treat various cancers. The clinical use of theranostics has increased in recent years, with U.S. Food and Drug Administration (FDA) approval of lutetium 177 (Lu) tetraazacyclododecane tetraacetic acid octreotate (DOTATATE) and Lu-prostate-specific membrane antigen vector-based radionuclide therapies. The field of theranostics has imminent potential for emerging clinical applications. This article reviews critical areas of active clinical advancement in theranostics, including forthcoming clinical trials advancing FDA-approved and emerging radiopharmaceuticals, approaches to dosimetry calculations, imaging of different radionuclide therapies, expanded indications for currently used theranostic agents to treat a broader array of cancers, and emerging ideas in the field. Molecular Imaging, Molecular Imaging-Cancer, Molecular Imaging-Clinical Translation, Molecular Imaging-Target Development, PET/CT, SPECT/CT, Radionuclide Therapy, Dosimetry, Oncology, Radiobiology © RSNA, 2023.
Topics: United States; Male; Humans; Precision Medicine; Radiopharmaceuticals; Positron Emission Tomography Computed Tomography; Radioisotopes; Neoplasms
PubMed: 37477566
DOI: 10.1148/rycan.220157 -
International Journal of Molecular... Jul 2023Non-targeted effects (NTE) have been generally regarded as a low-dose ionizing radiation (IR) phenomenon. Recently, regarding long distant abscopal effects have also... (Review)
Review
Non-targeted effects (NTE) have been generally regarded as a low-dose ionizing radiation (IR) phenomenon. Recently, regarding long distant abscopal effects have also been observed at high doses of IR) relevant to antitumor radiation therapy. IR is inducing NTE involving intracellular and extracellular signaling, which may lead to short-ranging bystander effects and distant long-ranging extracellular signaling abscopal effects. Internal and "spontaneous" cellular stress is mostly due to metabolic oxidative stress involving mitochondrial energy production (ATP) through oxidative phosphorylation and/or anaerobic pathways accompanied by the leakage of O and other radicals from mitochondria during normal or increased cellular energy requirements or to mitochondrial dysfunction. Among external stressors, ionizing radiation (IR) has been shown to very rapidly perturb mitochondrial functions, leading to increased energy supply demands and to ROS/NOS production. Depending on the dose, this affects all types of cell constituents, including DNA, RNA, amino acids, proteins, and membranes, perturbing normal inner cell organization and function, and forcing cells to reorganize the intracellular metabolism and the network of organelles. The reorganization implies intracellular cytoplasmic-nuclear shuttling of important proteins, activation of autophagy, and mitophagy, as well as induction of cell cycle arrest, DNA repair, apoptosis, and senescence. It also includes reprogramming of mitochondrial metabolism as well as genetic and epigenetic control of the expression of genes and proteins in order to ensure cell and tissue survival. At low doses of IR, directly irradiated cells may already exert non-targeted effects (NTE) involving the release of molecular mediators, such as radicals, cytokines, DNA fragments, small RNAs, and proteins (sometimes in the form of extracellular vehicles or exosomes), which can induce damage of unirradiated neighboring bystander or distant (abscopal) cells as well as immune responses. Such non-targeted effects (NTE) are contributing to low-dose phenomena, such as hormesis, adaptive responses, low-dose hypersensitivity, and genomic instability, and they are also promoting suppression and/or activation of immune cells. All of these are parts of the main defense systems of cells and tissues, including IR-induced innate and adaptive immune responses. The present review is focused on the prominent role of mitochondria in these processes, which are determinants of cell survival and anti-tumor RT.
Topics: DNA Damage; Radiation, Ionizing; DNA Repair; Mitochondria; Bystander Effect; Cytokines
PubMed: 37511215
DOI: 10.3390/ijms241411460 -
Radiotherapy and Oncology : Journal of... Nov 2023Voxel-based analysis (VBA) allows the full, 3-dimensional, dose distribution to be considered in radiotherapy outcome analysis. This provides new insights into... (Review)
Review
Voxel-based analysis (VBA) allows the full, 3-dimensional, dose distribution to be considered in radiotherapy outcome analysis. This provides new insights into anatomical variability of pathophysiology and radiosensitivity by removing the need for a priori definition of organs assumed to drive the dose response associated with patient outcomes. This approach may offer powerful biological insights demonstrating the heterogeneity of the radiobiology across tissues and potential associations of the radiotherapy dose with further factors. As this methodological approach becomes established, consideration needs to be given to translating VBA results to clinical implementation for patient benefit. Here, we present a comprehensive roadmap for VBA clinical translation. Technical validation needs to demonstrate robustness to methodology, where clinical validation must show generalisability to external datasets and link to a plausible pathophysiological hypothesis. Finally, clinical utility requires demonstration of potential benefit for patients in order for successful translation to be feasible. For each step on the roadmap, key considerations are discussed and recommendations provided for best practice.
PubMed: 37683811
DOI: 10.1016/j.radonc.2023.109868 -
Endocrine Oncology (Bristol, England) Jan 2024The field of nuclear theranostic clinical trials is continuously expanding as an increasing number of novel agents and treatment combinations are explored for treating... (Review)
Review
The field of nuclear theranostic clinical trials is continuously expanding as an increasing number of novel agents and treatment combinations are explored for treating advanced and metastatic cancers. Moving from 'bench-to-bedside' is oftentimes a complex and lengthy process. The objective of this overview is to explore the basic elements involved in designing clinical trials with a special focus on theranostics in nuclear medicine. The 'bench-to-bedside' journey involves translating basic scientific research into patient-effective treatments. Preclinical studies, a crucial initial step, are a complex process encompassing experiments, studies, and animal models to explore hypotheses in humans. Clinical trials follow, with predefined phases assessing safety, effectiveness, and comparisons to existing treatments. This process demands investments in data management, statistics, good clinical practice (GCP) accreditations, and collaborative efforts for funding and sustainable pricing. Theranostics, merging diagnostics and personalized treatment, is at the forefront. Continuous efforts to enhance existing agents involve reducing adverse effects, exploring new indications, and incorporating advanced imaging modalities. Radionuclide therapy, unique with non-uniform distribution and complex radiobiology, plays a distinct role. This article explores trends and challenges in each clinical trial phase in light of the emerging field of theranostics in nuclear medicine, emphasizing meticulous trial design, dosimetry optimization, and the necessity of collaborative stakeholder efforts for successful implementation.
PubMed: 38770190
DOI: 10.1530/EO-23-0045 -
Journal of Medical Physics 2023Radiosurgery and stereotactic radiotherapy have established themselves as precise and accurate areas of radiation oncology for the treatment of brain and extracranial... (Review)
Review
Radiosurgery and stereotactic radiotherapy have established themselves as precise and accurate areas of radiation oncology for the treatment of brain and extracranial lesions. Along with the evolution of other methods of radiotherapy, this type of treatment has been associated with significant advances in terms of a variety of modalities and techniques to improve the accuracy and efficacy of treatment. This paper provides a comprehensive overview of the progress in stereotactic radiosurgery (SRS) over several decades, and includes a review of various articles and research papers, commencing with the emergence of stereotactic techniques in radiotherapy. Key clinical aspects of SRS, such as fixation methods, radiobiology considerations, quality assurance practices, and treatment planning strategies, are presented. In addition, the review highlights the technological advancements in treatment modalities, encompassing the transition from cobalt-based systems to linear accelerator-based modalities. By addressing these topics, this study aims to offer insights into the advancements that have shaped the field of SRS, that have ultimately enhanced the accuracy and effectiveness of treatment.
PubMed: 38223793
DOI: 10.4103/jmp.jmp_62_23 -
Epigenomics Jul 2023COVID-19 is a viral respiratory infection induced by the newly discovered coronavirus SARS-CoV-2. miRNA is an example of a strong and direct regulator of a gene's... (Review)
Review
COVID-19 is a viral respiratory infection induced by the newly discovered coronavirus SARS-CoV-2. miRNA is an example of a strong and direct regulator of a gene's transcriptional activity. The interaction between miRNAs and their target molecules is responsible for homeostasis. Virus-derived and host-derived miRNAs are involved in the activity of hiding from immune system cells, inducing the inflammatory reaction through interplay with associated genes, during SARS-COV-2 infection. Interest in miRNAs has raised the comprehension of the machinery and pathophysiology of SARS-COV-2 infection. In this review, the effects and biological roles of miRNAs on SARS-CoV-2 pathogenicity and life cycle are described. The therapeutic potential of miRNAs against SARS-CoV-2 infection are also mentioned.
Topics: Humans; MicroRNAs; COVID-19; SARS-CoV-2; Inflammation
PubMed: 37661862
DOI: 10.2217/epi-2023-0179 -
Materials Horizons Oct 2023Radiotherapy is a key pillar of solid cancer treatment. Despite a high level of conformal dose deposition, radiotherapy is limited due to co-irradiation of organs at... (Review)
Review
Radiotherapy is a key pillar of solid cancer treatment. Despite a high level of conformal dose deposition, radiotherapy is limited due to co-irradiation of organs at risk and subsequent normal tissue toxicities. Nanotechnology offers an attractive opportunity for increasing the efficacy and safety of cancer radiotherapy. Leveraging the freedom of design and the growing synthetic capabilities of the nanomaterial-community, a variety of engineered nanomaterials have been designed and investigated as radiosensitizers or radioenhancers. While research so far has been primarily focused on gold nanoparticles and other high atomic number materials to increase the absorption cross section of tumor tissue, recent studies are challenging the traditional concept of high- nanoparticle radioenhancers and highlight the importance of catalytic activity. This review provides a concise overview on the knowledge of nanoparticle radioenhancement mechanisms and their quantification. It critically discusses potential radioenhancer candidate materials and general design criteria for different radiation therapy modalities, and concludes with research priorities in order to advance the development of nanomaterials, to enhance the efficacy of radiotherapy and to increase at the same time the therapeutic window.
Topics: Metal Nanoparticles; Gold; Radiation-Sensitizing Agents; Nanotechnology; Nanostructures
PubMed: 37555747
DOI: 10.1039/d3mh00265a -
Biomedicines Jul 2023The lunar dust problem was first formulated in 1969 with NASA's first successful mission to land a human being on the surface of the Moon. Subsequent Apollo missions... (Review)
Review
The lunar dust problem was first formulated in 1969 with NASA's first successful mission to land a human being on the surface of the Moon. Subsequent Apollo missions failed to keep the dust at bay, so exposure to the dust was unavoidable. In 1972, Harrison Schmitt suffered a brief sneezing attack, red eyes, an itchy throat, and congested sinuses in response to lunar dust. Some additional Apollo astronauts also reported allergy-like symptoms after tracking dust into the lunar module. Immediately following the Apollo missions, research into the toxic effects of lunar dust on the respiratory system gained a lot of interest. Moreover, researchers believed other organ systems might be at risk, including the skin and cornea. Secondary effects could translocate to the cardiovascular system, the immune system, and the brain. With current intentions to return humans to the moon and establish a semi-permanent presence on or near the moon's surface, integrated, end-to-end dust mitigation strategies are needed to enable sustainable lunar presence and architecture. The characteristics and formation of Martian dust are different from lunar dust, but advances in the research of lunar dust toxicity, mitigation, and protection strategies can prove strategic for future operations on Mars.
PubMed: 37509559
DOI: 10.3390/biomedicines11071921