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Journal of Clinical Medicine Dec 2022Copper is required for cancer cell proliferation and tumor angiogenesis. Copper-64 radionuclide (Cu), a form of copper chloride (CuCl), is rapidly emerging as a... (Review)
Review
Copper is required for cancer cell proliferation and tumor angiogenesis. Copper-64 radionuclide (Cu), a form of copper chloride (CuCl), is rapidly emerging as a diagnostic PET/CT tracer in oncology. It may also represent an interesting alternative to gallium-68 (Ga) as a radionuclide precursor for labelling radiopharmaceuticals used to investigate neuroendocrine tumors and prostate cancer. This emerging interest is also related to the nuclear properties of CuCl that make it an ideal theragnostic nuclide. Indeed, CuCl emits β and β particles together with high-linear-energy-transfer Auger electrons, suggesting the therapeutic potential of CuCl for the radionuclide cancer therapy of copper-avid tumors. Recently, CuCl was successfully used to image prostate cancer, bladder cancer, glioblastoma multiforme (GBM), and non-small cell lung carcinoma in humans. Copper cancer uptake was related to the expression of human copper transport 1 (hCTR1) on the cancer cell surface. Biodistribution, toxicology and radiation safety studies showed its radiation and toxicology safety. Based on the findings from the preclinical research studies, CuCl PET/CT also holds potential for the diagnostic imaging of human hepatocellular carcinoma (HCC), malignant melanoma, and the detection of the intracranial metastasis of copper-avid tumors based on the low physiological background of radioactive copper uptake in the brain.
PubMed: 36615024
DOI: 10.3390/jcm12010223 -
Cell Reports. Medicine Sep 2021In the current issue of , Lan et al. demonstrate that a bifunctional fusion protein targeting TGF-β and PD-L1 can synergize with radiation therapy to simultaneously...
In the current issue of , Lan et al. demonstrate that a bifunctional fusion protein targeting TGF-β and PD-L1 can synergize with radiation therapy to simultaneously augment tumor control and reduce normal tissue toxicity.
Topics: B7-H1 Antigen; Humans; Neoplasms; Transforming Growth Factor beta
PubMed: 34622240
DOI: 10.1016/j.xcrm.2021.100406 -
Environmental Health : a Global Access... Jun 2021Exposure to ionizing radiation has been associated with insulin resistance and type 2 diabetes. In light of recent work showing an association between ambient...
BACKGROUND
Exposure to ionizing radiation has been associated with insulin resistance and type 2 diabetes. In light of recent work showing an association between ambient particulate matter (PM) gross β-activity and gestational diabetes mellitus (GDM) among pregnant women, we examined pregnancy glucose levels in relation to PM gross β-activity to better understand this pathway.
METHODS
Our study included 103 participants receiving prenatal care at Beth Israel Deaconess Medical Center in Boston, MA. PM gross β-activity was obtained from US Environmental Protection Agency's RadNet program monitors, and blood glucose levels were obtained from the non-fasting glucose challenge test performed clinically as the first step of the 2-step GDM screening test. For each exposure window we examined (i.e., moving average same-day, one-week, first-trimester, and second-trimester PM gross β-activity), we fitted generalized additive models and adjusted for clinical characteristics, socio-demographic factors, temporal variables, and PM with an aerodynamic diameter ≤ 2.5 μm (PM). Subgroup analyses by maternal age and by body mass index were also conducted.
RESULTS
An interquartile range increase in average PM gross β-activity during the second trimester of pregnancy was associated with an increase of 17.5 (95% CI: 0.8, 34.3) mg/dL in glucose concentration. Associations were stronger among younger and overweight/obese participants. Our findings also suggest that the highest compared to the lowest quartile of one-week exposure was associated with 17.0 (95% CI: - 4.0, 38.0) mg/dL higher glucose levels. No associations of glucose were observed with PM gross β-activity during same-day and first-trimester exposure windows. PM was not associated with glucose levels during any exposure window in our data.
CONCLUSIONS
Exposure to higher levels of ambient PM gross β-activity was associated with higher blood glucose levels in pregnant patients, with implications for how this novel environmental factor could impact pregnancy health.
Topics: Adult; Air Pollutants; Beta Particles; Blood Glucose; Female; Humans; Maternal Exposure; Particulate Matter; Pregnancy
PubMed: 34126994
DOI: 10.1186/s12940-021-00744-9 -
Frontiers in Immunology 2023Intestinal epithelial cells (IECs) are the first to encounter luminal microorganisms and actively participate in intestinal immunity. We reported that IECs express the...
BACKGROUND
Intestinal epithelial cells (IECs) are the first to encounter luminal microorganisms and actively participate in intestinal immunity. We reported that IECs express the β-glucan receptor Dectin-1, and respond to commensal fungi and β-glucans. In phagocytes, Dectin-1 mediates LC3-associated phagocytosis (LAP) utilizing autophagy components to process extracellular cargo. Dectin-1 can mediate phagocytosis of β-glucan-containing particles by non-phagocytic cells. We aimed to determine whether human IECs phagocytose β-glucan-containing fungal particles LAP.
METHODS
Colonic (n=18) and ileal (n=4) organoids from individuals undergoing bowel resection were grown as monolayers. Fluorescent-dye conjugated zymosan (β-glucan particle), heat-killed- and UV inactivated were applied to differentiated organoids and to human IEC lines. Confocal microscopy was used for live imaging and immuno-fluorescence. Quantification of phagocytosis was carried out with a fluorescence plate-reader.
RESULTS
zymosan and particles were phagocytosed by monolayers of human colonic and ileal organoids and IEC lines. LAP was identified by LC3 and Rubicon recruitment to phagosomes and lysosomal processing of internalized particles was demonstrated by co-localization with lysosomal dyes and LAMP2. Phagocytosis was significantly diminished by blockade of Dectin-1, actin polymerization and NAPDH oxidases.
CONCLUSIONS
Our results show that human IECs sense luminal fungal particles and internalize them LAP. This novel mechanism of luminal sampling suggests that IECs may contribute to the maintenance of mucosal tolerance towards commensal fungi.
Topics: Humans; beta-Glucans; Epithelial Cells; Fungi; Phagocytosis; Zymosan
PubMed: 36969163
DOI: 10.3389/fimmu.2023.1142492 -
Laboratory Investigation; a Journal of... Mar 2022Pancreatic cancer (PC) is highly resistant to chemo and radiotherapy. Radiation-induced fibrosis (RIF) is a major cause of clinical concern for various malignancies,...
Pancreatic cancer (PC) is highly resistant to chemo and radiotherapy. Radiation-induced fibrosis (RIF) is a major cause of clinical concern for various malignancies, including PC. In this study, we aimed to evaluate the radiosensitizing and anti-RIF potential of fluvastatin in PC. Short-term viability and clonogenic survival assays were used to evaluate the radiosensitizing potential of fluvastatin in multiple human and murine PC cell lines. The expression of different proteins was analyzed to understand the mechanisms of fluvastatin-mediated radiosensitization of PC cells and its anti-RIF effects in both mouse and human pancreatic stellate cells (PSCs). Finally, these effects of fluvastatin and/or radiation were assessed in an immune-competent syngeneic murine model of PC. Fluvastatin radiosensitized multiple PC cell lines, as well as radioresistant cell lines in vitro, by inhibiting radiation-induced DNA damage repair response. Nonmalignant cells, such as PSCs and NIH3T3 cells, were less sensitive to fluvastatin-mediated radiosensitization than PC cells. Interestingly, fluvastatin suppressed radiation and/or TGF-β-induced activation of PSCs, as well as the fibrogenic properties of these cells in vitro. Fluvastatin considerably augmented the antitumor effect of external radiation therapy and also suppressed intra-tumor RIF in vivo. These findings suggested that along with radiation, fluvastatin co-treatment may be a potential therapeutic approach against PC.
Topics: Animals; Apoptosis; Autophagy; Cell Line, Tumor; Cell Survival; Cells, Cultured; Embryo, Nonmammalian; Fibrosis; Fluvastatin; Humans; Mice; Mice, Inbred C57BL; NIH 3T3 Cells; Neoplasms, Experimental; Pancreatic Neoplasms; Radiation Tolerance; Transforming Growth Factor beta; Zebrafish
PubMed: 34773069
DOI: 10.1038/s41374-021-00690-7 -
EJNMMI Radiopharmacy and Chemistry Aug 2019Over the years, a broad spectrum of applications of the radionuclide holmium-166 as a medical isotope has been established. The isotope holmium-166 is attractive as it... (Review)
Review
Over the years, a broad spectrum of applications of the radionuclide holmium-166 as a medical isotope has been established. The isotope holmium-166 is attractive as it emits high-energy beta radiation which can be used for a therapeutic effect and gamma radiation which can be used for nuclear imaging purposes. Furthermore, holmium-165 can be visualized by MRI because of its paramagnetic properties and by CT because of its high density. Since holmium-165 has a natural abundance of 100%, the only by-product is metastable holmium-166 and no costly chemical purification steps are necessary for production of nuclear reactor derived holmium-166. Several compounds labelled with holmium-166 are now used in patients, such Ho-labelled microspheres for liver malignancies, Ho-labelled chitosan for hepatocellular carcinoma (HCC) and [Ho]Ho DOTMP for bone metastases. The outcomes in patients are very promising, making this isotope more and more interesting for applications in interventional oncology. Both drugs as well as medical devices labelled with radioactive holmium are used for internal radiotherapy. One of the treatment possibilities is direct intratumoural treatment, in which the radioactive compound is injected with a needle directly into the tumour. Numerous other applications have been developed, like patches for treatment of skin cancer and holmium labelled antibodies and peptides. The second major application that is currently clinically applied is selective internal radiation therapy (SIRT, also called radioembolization), a novel treatment option for liver malignancies. This review discusses medical drugs and medical devices based on the therapeutic radionuclide holmium-166.
PubMed: 31659560
DOI: 10.1186/s41181-019-0066-3 -
Molecules (Basel, Switzerland) Aug 2022Advances in the field of molecular biology have had an impact on biomedical applications, which provide greater hope for both imaging and therapeutics. Work has been... (Review)
Review
Advances in the field of molecular biology have had an impact on biomedical applications, which provide greater hope for both imaging and therapeutics. Work has been intensified on the development of radionuclides and their application in radiopharmaceuticals (RP) which will certainly influence and expand therapeutic approaches in the future treatment of patients. Alpha or beta particles and Auger electrons are used for therapy purposes, and each has advantages and disadvantages. The radionuclides labeled drug delivery system will deliver the particles to the specific targeting cell. Different radioligands can be chosen to uniquely target molecular receptors or intracellular components, making them suitable for personal patient-tailored therapy in modern cancer therapy management. Advances in nanotechnology have enabled nanoparticle drug delivery systems that can allow for specific multivalent attachment of targeted molecules of antibodies, peptides, or ligands to the surface of nanoparticles for therapy and imaging purposes. This review presents fundamental radionuclide properties with particular reference to tumor biology and receptor characteristic of radiopharmaceutical targeted therapy development.
Topics: Beta Particles; Diagnostic Imaging; Humans; Neoplasms; Radioisotopes; Radiopharmaceuticals
PubMed: 36014472
DOI: 10.3390/molecules27165231 -
Biomolecules Sep 2022Research has proven that light treatment, specifically red light radiation, can provide more clinical benefits to human health. Our investigation was firstly conducted...
Research has proven that light treatment, specifically red light radiation, can provide more clinical benefits to human health. Our investigation was firstly conducted to characterize the tissue morphology of mouse breast post 660 nm laser radiation with low power and long-term exposure. RNA sequencing results revealed that light exposure with a higher intervention dosage could cause a number of differentially expressed genes compared with a low intervention dosage. Gene ontology analysis, protein-protein interaction network analysis, and gene set enrichment analysis results suggested that 660 nm light exposure can activate more transcription-related pathways in HC11 breast epithelial cells, and these pathways may involve modulating critical gene expression. To consider the critical role of the Wnt/T-catenin pathway in light-induced modulation, we hypothesized that this pathway might play a major role in response to 660 nm light exposure. To validate our hypothesis, we conducted qRT-PCR, immunofluorescence staining, and Western blot assays, and relative results corroborated that laser radiation could promote expression levels of β-catenin and relative phosphorylation. Significant changes in metabolites and pathway analysis revealed that 660 nm laser could affect nucleotide metabolism by regulating purine metabolism. These findings suggest that the Wnt/β-catenin pathway may be the major sensor for 660 nm laser radiation, and it may be helpful to rescue drawbacks or side effects of 660 nm light exposure through relative interventional agents.
Topics: Humans; Mice; Animals; beta Catenin; Lipid Metabolism; Epithelium; Lasers; Nucleotides; Purines
PubMed: 36291598
DOI: 10.3390/biom12101389 -
Pathogens (Basel, Switzerland) Feb 2022The handling of highly pathogenic viruses, whether for diagnostic or research purposes, often requires an inactivation step. This article reviews available inactivation... (Review)
Review
The handling of highly pathogenic viruses, whether for diagnostic or research purposes, often requires an inactivation step. This article reviews available inactivation techniques published in peer-reviewed journals and their benefits and limitations in relation to the intended application. The bulk of highly pathogenic viruses are represented by enveloped RNA viruses belonging to the , , , , , , , and families. Here, we summarize inactivation methods for these virus families that allow for subsequent molecular and serological analysis or vaccine development. The techniques identified here include: treatment with guanidium-based chaotropic salts, heat inactivation, photoactive compounds such as psoralens or 1.5-iodonaphtyl azide, detergents, fixing with aldehydes, UV-radiation, gamma irradiation, aromatic disulfides, beta-propiolacton and hydrogen peroxide. The combination of simple techniques such as heat or UV-radiation and detergents such as Tween-20, Triton X-100 or Sodium dodecyl sulfate are often sufficient for virus inactivation, but the efficiency may be affected by influencing factors including quantity of infectious particles, matrix constitution, pH, salt- and protein content. Residual infectivity of the inactivated virus could have disastrous consequences for both laboratory/healthcare personnel and patients. Therefore, the development of inactivation protocols requires careful considerations which we review here.
PubMed: 35215213
DOI: 10.3390/pathogens11020271 -
International Journal of Environmental... Jun 2021This study aimed to examine factors affecting radiation protection behaviors among emergency room nurses by assessing knowledge about radiation protection and attitude...
This study aimed to examine factors affecting radiation protection behaviors among emergency room nurses by assessing knowledge about radiation protection and attitude towards radiation protection, employing a cross-sectional design. Subjects were a convenience sample of 129 nurses working in the emergency rooms of three advanced general hospitals. Data were collected using self-report questionnaires and analyzed using -test, ANOVA, Pearson correlation coefficients, and multiple regression. There were significant relations between knowledge about radiation protection and attitude towards radiation protection (r = 0.34, < 0.001), knowledge about radiation protection and radiation protection behaviors (r = 0.37, < 0.001), and attitude towards radiation protection and radiation protection behaviors (r = 0.33, < 0.001). The factors affecting radiation protection behaviors were radiation protection knowledge (β = 0.12, = 0.045), attitude towards radiation protection (β = 0.17, = 0.009), the experience of radiation protection education (β = 0.27, < 0.001), and wearing of protective equipment (β = 0.29, < 0.001). The governments, hospital administrators, and radiation protection agencies should strengthen their radiation defense environment to protect emergency room nurses from radiation. Research and development of radiation defense equipment and the medical examination of emergency room nurses should be carried out, radiation defense behavior protocols should be developed, radiation defense education opportunities should be provided, and the use of defense equipment should be encouraged.
Topics: Attitude of Health Personnel; Cross-Sectional Studies; Emergency Service, Hospital; Health Knowledge, Attitudes, Practice; Humans; Nurses; Nursing Staff, Hospital; Radiation Protection; Surveys and Questionnaires
PubMed: 34207672
DOI: 10.3390/ijerph18126238