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Cureus May 2024Primary central nervous system (CNS) lymphoma is a rare and aggressive form of extranodal non-Hodgkin's lymphoma, limited to the brain, eyes, spinal cord, or...
Primary central nervous system (CNS) lymphoma is a rare and aggressive form of extranodal non-Hodgkin's lymphoma, limited to the brain, eyes, spinal cord, or leptomeninges without systemic involvement. This group of malignant tumors is characterized by a particular diagnostic, therapeutic, and evolutionary profile compared to other types of non-Hodgkin's lymphomas. We report a case of a young patient treated in our university hospital center for primary cerebral lymphoma who benefited from primary chemotherapy and then consolidation radiotherapy with good disease control and good tolerance.
PubMed: 38939239
DOI: 10.7759/cureus.61219 -
Vaccines Jun 2024Therapeutic modified mRNAs are being developed for a broad range of human diseases. However, the impact of potential miscoding of modified mRNAs on self-tolerance...
Therapeutic modified mRNAs are being developed for a broad range of human diseases. However, the impact of potential miscoding of modified mRNAs on self-tolerance remains unknown. Additionally, more studies are needed to explore the effects of nucleoside alkylation on translation. While all six tested modifications are tolerated as substrates by T7 RNA polymerase and inhibited mRNA immunogenicity, the translation efficiency varied significantly depending on the type of modification. In contrast to methylation, ethylation at the N1 position of pseudouridine (Ψ) hindered translation, suggesting that the C5-C1' glycosidic bond alone is not a critical element for high translation. Inhibition of mRNA translation was also observed with 5-methoxyuridine modification. However, this inhibition was partially alleviated through the optimization of mRNA coding sequences. BALB/c mice immunized with syngeneic ψ-modified mRNA encoding for Wilms' tumor antigen-1 (WT1) developed a low but significant level of anti-WT1 IgG antibodies compared to those immunized with either unmodified or N1-methyl ψ-modified mRNA. Overall, the data indicate that adding a simple ethyl group (-CHCH) at the N1 position of ψ has a major negative effect on translation despite its reduced immunogenicity. Additionally, mRNA containing Ψ may alter translation fidelity at certain codons, which could lead to a breakdown of immune tolerance to self-antigens. This concern should be taken into account during gene replacement therapies, although it could benefit mRNA-based vaccines by generating a diverse repertoire of antigens.
PubMed: 38932353
DOI: 10.3390/vaccines12060624 -
International Journal of Molecular... Jun 2024Application of laser-generated electron beams in radiotherapy is a recent development. Accordingly, mechanisms of biological response to radiation damage need to be...
Application of laser-generated electron beams in radiotherapy is a recent development. Accordingly, mechanisms of biological response to radiation damage need to be investigated. In this study, telomere length (TL) as endpoint of genetic damage was analyzed in human blood cells (leukocytes) and K562 leukemic cells irradiated with laser-generated ultrashort electron beam. Metaphases and interphases were analyzed in quantitative fluorescence in situ hybridization (Q-FISH) to assess TL. TLs were shortened compared to non-irradiated controls in both settings (metaphase and interphase) after irradiation with 0.5, 1.5, and 3.0 Gy in blood leukocytes. Radiation also caused a significant TL shortening detectable in the interphase of K562 cells. Overall, a negative correlation between TL and radiation doses was observed in normal and leukemic cells in a dose-dependent manner. K562 cells were more sensitive than normal blood cells to increasing doses of ultrashort electron beam radiation. As telomere shortening leads to genome instability and cell death, the results obtained confirm the suitability of this biomarker for assessing genotoxic effects of accelerated electrons for their further use in radiation therapy. Observed differences in TL shortening between normal and K562 cells provide an opportunity for further development of optimal radiation parameters to reduce side effects in normal cells during radiotherapy.
Topics: Humans; K562 Cells; Leukocytes; Electrons; Telomere; Leukemia; Telomere Homeostasis; In Situ Hybridization, Fluorescence; Telomere Shortening; DNA Damage; Dose-Response Relationship, Radiation
PubMed: 38928414
DOI: 10.3390/ijms25126709 -
Radiation Oncology (London, England) Jun 2024At present, it has been found that many patients have acquired resistance to radiotherapy, which greatly reduces the effect of radiotherapy and further affects the...
BACKGROUND
At present, it has been found that many patients have acquired resistance to radiotherapy, which greatly reduces the effect of radiotherapy and further affects the prognosis. CircRNAs is involved in the regulation of radiosensitivity of many kinds of tumor cells. Therefore, the main purpose of this study is to explore the regulatory effect of CircRNA_101491 on radiosensitivity of ESCC and its related mechanism.
METHODS
We established ESCC radiation-resistant cell line (KYSE150R cell) by gradient dose method, and tested the difference of KYSE150 between KYSE150R cell and parent cell in vitro. Then, after knocking down the expression of CircRNA_101491, a series of in vitro experiments were conducted to verify the effects of CircRNA_101491 on the phenotype and radiosensitivity of KYSE150R cells, and further analyzed the related regulatory mechanism. In addition, we also used the model of transplanted tumor in nude mice to investigate the effect of CircRNA_101491 on the radiosensitivity of ESCC in vivo.
RESULTS
According to a series of in vitro experiments, we confirmed that KYSE150R cells lost the epithelial phenotype and obtained interstitial cell-like phenotype, and found that CircRNA_101491 was highly expressed in KYSE150R cells. In addition, we found that knocking down the expression of CircRNA_101491 will lift the inhibition of miR-125a-5p, and then reverse the process of EMT, accelerate the process of apoptosis, thus play a role in radiosensitization. The in vivo experiment of transplanted tumor in nude mice also showed that knocking down the expression of CircRNA_101491 could enhance the radiosensitivity of ESCC.
CONCLUSION
In conclusion, we confirmed that interfering with the expression of CircRNA_101491 can relieve the inhibition of miR-125a-5p, thus reverse the process of interstitial phenotype, accelerate the process of apoptosis, and enhance the radiosensitivity of ESCC.
Topics: MicroRNAs; Radiation Tolerance; Animals; RNA, Circular; Humans; Mice; Esophageal Neoplasms; Mice, Nude; Esophageal Squamous Cell Carcinoma; Apoptosis; Cell Proliferation; Gene Expression Regulation, Neoplastic; Mice, Inbred BALB C; Cell Line, Tumor; Xenograft Model Antitumor Assays; Tumor Cells, Cultured
PubMed: 38926729
DOI: 10.1186/s13014-024-02478-7 -
Scientific Reports Jun 2024Ultra-high dose rate (UHDR) irradiation has been shown to have a sparing effect on healthy tissue, an effect known as 'FLASH'. This effect has been studied across...
Ultra-high dose rate (UHDR) irradiation has been shown to have a sparing effect on healthy tissue, an effect known as 'FLASH'. This effect has been studied across several radiation modalities, including photons, protons and clinical energy electrons, however, very little data is available for the effect of FLASH with Very High Energy Electrons (VHEE). pBR322 plasmid DNA was used as a biological model to measure DNA damage in response to Very High Energy Electron (VHEE) irradiation at conventional (0.08 Gy/s), intermediate (96 Gy/s) and ultra-high dose rates (UHDR, (2 × 10 Gy/s) at the CERN Linear Electron Accelerator (CLEAR) user facility. UHDRs were used to determine if the biological FLASH effect could be measured in the plasmid model, within a hydroxyl scavenging environment. Two different concentrations of the hydroxyl radical scavenger Tris were used in the plasmid environment to alter the proportions of indirect damage, and to replicate a cellular scavenging capacity. Indirect damage refers to the interaction of ionising radiation with molecules and species to generate reactive species which can then attack DNA. UHDR irradiated plasmid was shown to have significantly reduced amounts of damage in comparison to conventionally irradiated, where single strand breaks (SSBs) was used as the biological endpoint. This was the case for both hydroxyl scavenging capacities. A reduced electron energy within the VHEE range was also determined to increase the DNA damage to pBR322 plasmid. Results indicate that the pBR322 plasmid model can be successfully used to explore and test the effect of UHDR regimes on DNA damage. This is the first study to report FLASH sparing with VHEE, with induced damage to pBR322 plasmid DNA as the biological endpoint. UHDR irradiated plasmid had reduced amounts of DNA single-strand breaks (SSBs) in comparison with conventional dose rates. The magnitude of the FLASH sparing was a 27% reduction in SSB frequency in a 10 mM Tris environment and a 16% reduction in a 100 mM Tris environment.
Topics: Plasmids; DNA Damage; Electrons; Dose-Response Relationship, Radiation; Humans; Particle Accelerators; DNA Breaks, Single-Stranded
PubMed: 38926450
DOI: 10.1038/s41598-024-65055-8 -
Physiologia Plantarum 2024In recent years, there has been an increase in the study of phytomelatonin. Having numerous functions in animals, melatonin produced by plants (phytomelatonin) is also a... (Review)
Review
In recent years, there has been an increase in the study of phytomelatonin. Having numerous functions in animals, melatonin produced by plants (phytomelatonin) is also a multi-regulatory molecule with great potential in plant physiology and in mitigating abiotic stresses, such as drought, salinity, chilling, heat, chemical contamination, and UV-radiation stress. This review highlights the primary functions of phytomelatonin as an anti-stress molecule against abiotic stress. We discuss the role of phytomelatonin as a master regulator, oxidative stress manager, reactive oxygen species and reactive nitrogen species regulator, and defense compounds inducer. Although there exist a handful of reviews on the crosstalk of phytomelatonin with other signaling molecules like auxin, cytokinin, gibberellin, abscisic acid, ethylene, nitric oxide, jasmonic acid, and salicylic acid, this review looks at studies that have reported a few aspects of phytomelatonin with newly discovered signaling molecules along with classical signaling molecules with relation to abiotic stress tolerance. The research and applications of phytomelatonin with hydrogen sulfide, strigolactones, brassinosteroids, and polyamines are still in their nascent stage but hold a promising scope for the future. Additionally, this review states the recent developments in the signaling of phytomelatonin with nitrogen metabolism and nitrosative stress in plants.
Topics: Melatonin; Homeostasis; Stress, Physiological; Signal Transduction; Plants; Plant Physiological Phenomena; Plant Growth Regulators
PubMed: 38924553
DOI: 10.1111/ppl.14413 -
Biomedical Physics & Engineering Express Jun 2024: To summarize our institutional prostate stereotactic body radiation therapy (SBRT) experience using auto beam hold (ABH) technique for intrafractional prostate motion...
: To summarize our institutional prostate stereotactic body radiation therapy (SBRT) experience using auto beam hold (ABH) technique for intrafractional prostate motion and assess ABH tolerance of 10-millimeter (mm) diameter.: Thirty-two patients (160 fractions) treated using ABH technique between 01/2018 and 03/2021 were analyzed. During treatment, kV images were acquired every 20-degree gantry rotation to visualize 3-4 gold fiducials within prostate to track target motion. If the fiducial center fell outside the tolerance circle (diameter = 10 mm), beam was automatically turned off for reimaging and repositioning. Number of beam holds and couch translational movement magnitudes were recorded. Dosimetric differences from intrafractional motion were calculated by shifting planned isocenter.: Couch movement magnitude (mean ± SD) in vertical, longitudinal and lateral directions were -0.7 ± 2.5, 1.4 ± 2.9 and -0.1 ± 0.9 mm, respectively. For most fractions (77.5%), no correction was necessary. Number of fractions requiring one, two, or three corrections were 15.6%, 5.6% and 1.3%, respectively. Of the 49 corrections, couch shifts greater than 3 mm were seen primarily in the vertical (31%) and longitudinal (39%) directions; corresponding couch shifts greater than 5 mm occurred in 2% and 6% of cases. Dosimetrically, 100% coverage decreased less than 2% for clinical target volume (CTV) (-1 ± 2%) and less than 10% for PTV (-10 ± 6%). Dose to bladder, bowel and urethra tended to increase (Bladder: ΔD10%:184 ± 466 cGy, ΔD40%:139 ± 241 cGy, Bowel: ΔD1 cm:54 ± 129 cGy; ΔD5 cm:44 ± 116 cGy, Urethra: ΔD0.03 cm:1 ± 1%). Doses to the rectum tended to decrease (Rectum: ΔD1 cm:-206 ± 564 cGy, ΔD10%:-97 ± 426 cGy; ΔD20%:-50 ± 251 cGy).: With the transition from conventionally fractionated intensity modulated radiation therapy to SBRT for localized prostate cancer treatment, it is imperative to ensure that dose delivery is spatially accurate for appropriate coverage to target volumes and limiting dose to surrounding organs. Intrafractional motion monitoring can be achieved using triggered imaging to image fiducial markers and ABH to allow for reimaging and repositioning for excessive motion.
Topics: Humans; Male; Prostatic Neoplasms; Radiosurgery; Prostate; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiometry; Movement; Fiducial Markers; Motion; Dose Fractionation, Radiation; Radiotherapy, Intensity-Modulated; Urinary Bladder; Rectum; Organs at Risk
PubMed: 38923907
DOI: 10.1088/2057-1976/ad4b1d -
Radiation Oncology (London, England) Jun 2024Magnetic resonance guided radiotherapy (MRgRT) allows daily adaptation of treatment plans to compensate for positional changes of target volumes and organs at risk...
INTRODUCTION
Magnetic resonance guided radiotherapy (MRgRT) allows daily adaptation of treatment plans to compensate for positional changes of target volumes and organs at risk (OARs). However, current adaptation times are relatively long and organ movement occurring during the adaptation process might offset the benefit gained by adaptation. The aim of this study was to evaluate the dosimetric impact of these intrafractional changes. Additionally, a method to predict the extent of organ movement before the first treatment was evaluated in order to have the possibility to compensate for them, for example by adding additional margins to OARs.
MATERIALS & METHODS
Twenty patients receiving adaptive MRgRT for treatment of abdominal lesions were retrospectively analyzed. Magnetic resonance (MR) images acquired at the start of adaptation and immediately before irradiation were used to calculate adapted and pre-irradiation dose in OARs directly next to the planning target volume. The extent of organ movement was determined on MR images acquired during simulation sessions and adaptive treatments, and their agreement was evaluated. Correlation between the magnitude of organ movement during simulation and the duration of simulation session was analyzed in order to assess whether organ movement might be relevant even if the adaptation process could be accelerated in the future.
RESULTS
A significant increase in dose constraint violations was observed from adapted (6.9%) to pre-irradiation (30.2%) dose distributions. Overall, OAR dose increased significantly by 4.3% due to intrafractional organ movement. Median changes in organ position of 7.5 mm (range 1.5-10.5 mm) were detected within a median time of 17.1 min (range 1.6-28.7 min). Good agreement was found between the range of organ movement during simulation and adaptation (66.8%), especially if simulation sessions were longer and multiple MR images were acquired. No correlation was determined between duration of simulation sessions and magnitude of organ movement.
CONCLUSION
Intrafractional organ movement can impact dose distributions and lead to violations of OAR tolerance doses, which impairs the benefit of daily on-table plan adaptation. By application of simulation images, the extent of intrafractional organ movement can be predicted, which possibly allows to compensate for them.
Topics: Humans; Radiotherapy, Image-Guided; Radiotherapy Planning, Computer-Assisted; Retrospective Studies; Organs at Risk; Magnetic Resonance Imaging; Radiotherapy Dosage; Abdominal Neoplasms; Female; Male; Middle Aged; Aged; Radiotherapy, Intensity-Modulated; Movement; Dose Fractionation, Radiation
PubMed: 38918828
DOI: 10.1186/s13014-024-02466-x -
Gastric Cancer : Official Journal of... Jun 2024For the elderly patients with gastric cancer, it may be more challenging to tolerate complete neoadjuvant therapy (NAT). The impact of discontinued NAT on the surgical...
Discontinuation of neoadjuvant therapy does not influence postoperative short-term outcomes in elderly patients (≥ 70 years) with resectable gastric cancer: a population-based study from the dutch upper gastrointestinal cancer audit (DUCA) data.
BACKGROUND
For the elderly patients with gastric cancer, it may be more challenging to tolerate complete neoadjuvant therapy (NAT). The impact of discontinued NAT on the surgical safety and pathological outcomes of elderly patients with poor tolerance remains poorly understood.
METHODS
Gastric cancer patients received gastrectomy with curative intent from the Dutch upper GI cancer audit (DUCA) database were included in this study. The independent association of age with not initiating and discontinuation of NAT was assessed with restricted cubic splines (RCS). According to the RCS results, age ≥ 70 years was defined as elderly. Short-term postoperative outcomes and pathological results were compared between elderly patients who completed and discontinued NAT.
RESULTS
Between 2011- 2021, total of 3049 patients were included. The risk of not initiating NAT increased from 70 years. In 1954 (64%) patients receiving NAT, the risk of discontinuation increased from 55 years, reaching the peak around 74 years. In the elderly, discontinued NAT was not independently associated with worse 30-day mortality, overall complications, anastomotic leakage, re-intervention, and pathologic complete response, but was associated with a higher risk of R1/2 resection (p-value = 0.001), higher ypT stage (p-value = 0.004), ypN + (p-value = 0.008), and non-response ( p-value = 0.012).
CONCLUSION
A decreased utilization of NAT has been observed in Dutch gastric cancer patients from 70 years due to old age considerations, possibly because of their high risk of discontinuation. Increasing the utilization of NAT may not adversely impact the surgical safety of gastric cancer population ≥ 70 years and may contribute to better pathological results.
PubMed: 38918269
DOI: 10.1007/s10120-024-01522-5 -
Supportive Care in Cancer : Official... Jun 2024Radical radiotherapy (RT) is the cornerstone of Head and Neck (H&N) cancer treatment, but it often leads to fatigue due to irradiation of brain structures, impacting... (Review)
Review
INTRODUCTIONS
Radical radiotherapy (RT) is the cornerstone of Head and Neck (H&N) cancer treatment, but it often leads to fatigue due to irradiation of brain structures, impacting patient quality of life.
OBJECTIVE
This study aimed to systematically investigate the dose correlates of fatigue after H&N RT in brain structures.
METHODS
The systematic review included studies that examined the correlation between fatigue outcomes in H&N cancer patients undergoing RT at different time intervals and brain structures. PubMed, Scopus, and WOS databases were used in the systematic review. A methodological quality assessment of the included studies was conducted following the PRISMA guidelines. After RT, the cohort of H&N cancer patients was analyzed for dose correlations with brain structures and substructures, such as the posterior fossa, brainstem, cerebellum, pituitary gland, medulla, and basal ganglia.
RESULT
Thirteen studies meeting the inclusion criteria were identified in the search. These studies evaluated the correlation between fatigue and RT dose following H&N RT. The RT dose ranged from 40 Gy to 70 Gy. Most of the studies indicated a correlation between the trajectory of fatigue and the dose effect, with higher levels of fatigue associated with increasing doses. Furthermore, five studies found that acute and late fatigue was associated with dose volume in specific brain structures, such as the brain stem, posterior fossa, cerebellum, pituitary gland, hippocampus, and basal ganglia.
CONCLUSION
Fatigue in H&N RT patients is related to the radiation dose received in specific brain areas, particularly in the posterior fossa, brain stem, cerebellum, pituitary gland, medulla, and basal ganglia. Dose reduction in these areas may help alleviate fatigue. Monitoring fatigue in high-risk patients after radiation therapy could be beneficial, especially for those experiencing late fatigue.
Topics: Humans; Head and Neck Neoplasms; Fatigue; Radiotherapy Dosage; Quality of Life; Dose-Response Relationship, Radiation; Brain
PubMed: 38918218
DOI: 10.1007/s00520-024-08655-4