-
Nature Communications Jun 2024Cancer resistance to immune checkpoint inhibitors motivated investigations into leveraging the immunostimulatory properties of radiotherapy to overcome immune evasion...
Cancer resistance to immune checkpoint inhibitors motivated investigations into leveraging the immunostimulatory properties of radiotherapy to overcome immune evasion and to improve treatment response. However, clinical benefits of radiotherapy-immunotherapy combinations have been modest. Routine concomitant tumor-draining lymph node irradiation (DLN IR) might be the culprit. As crucial sites for generating anti-tumor immunity, DLNs are indispensable for the in situ vaccination effect of radiotherapy. Simultaneously, DLN sparing is often not feasible due to metastatic spread. Using murine models of metastatic disease in female mice, here we demonstrate that delayed (adjuvant), but not neoadjuvant, DLN IR overcomes the detrimental effect of concomitant DLN IR on the efficacy of radio-immunotherapy. Moreover, we identify IR-induced disruption of the CCR7-CCL19/CCL21 homing axis as a key mechanism for the detrimental effect of DLN IR. Our study proposes delayed DLN IR as a strategy to maximize the efficacy of radio-immunotherapy across different tumor types and disease stages.
Topics: Animals; Immune Checkpoint Inhibitors; Female; Mice; Lymph Nodes; Cell Line, Tumor; Immunotherapy; Mice, Inbred C57BL; Lymphatic Irradiation; Disease Models, Animal; Combined Modality Therapy; Humans; Receptors, CCR7; Neoplasm Metastasis
PubMed: 38951172
DOI: 10.1038/s41467-024-49873-y -
Journal of Veterinary Research Jun 2024This study focuses on perfluoroalkyl substance (PFAS) content in chickens' eggs and the livers of farm animals.
INTRODUCTION
This study focuses on perfluoroalkyl substance (PFAS) content in chickens' eggs and the livers of farm animals.
MATERIAL AND METHODS
Chickens' eggs (n = 25) and the livers of cows (n = 10), chickens (n = 7) and horses (n = 3) were collected from various regions of Poland. Samples were analysed using the isotope dilution technique with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS).
RESULTS
The mean lower bound (LB) sum of four PFAS (∑4 PFAS) concentrations (perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorohexanesulfonic acid (PFHxS)) were the highest in cows' livers (0.52 μg/kg) and much lower in chickens' (0.17 μg/kg) and horses' livers (0.13 μg/kg) and chickens' eggs (0.096 μg/kg). The ratio of ∑4 PFASs to the limits set by Commission Regulation (EU) 2023/915 was <7% for liver and <6% for eggs. Linear PFOS was the compound with the highest detection frequency (8% in eggs and 48% in all livers). In cows' livers it was detected in 80% of samples. The estimated exposure to LB ∑4 PFASs consumption of liver tissue from farm animals (assuming 50 g and 100 g portions) was <52% of the tolerable weekly intake (TWI) for children and <17% of the TWI for adults. Dietary intake the average portion of three eggs led to low exposure of <15% for children and <5% for adults.
CONCLUSION
Neither eggs nor the livers of chickens or horses as analysed in this study are significant sources of PFASs, while cows' livers might contribute significantly to a child's overall dietary intake. Further investigation of PFOS in farm animal livers should be conducted.
PubMed: 38947157
DOI: 10.2478/jvetres-2024-0034 -
Journal of Veterinary Research Jun 2024Radioactive caesium-137 occurring in the environment may be taken up by plants and animals and pose a trophic threat to humans. Game animals living in forest ecosystems...
INTRODUCTION
Radioactive caesium-137 occurring in the environment may be taken up by plants and animals and pose a trophic threat to humans. Game animals living in forest ecosystems are very good bioindicators of the level of environmental contamination by ionising radiation. The main species measurably exposed to caesium-137 are the wild boar (), the roe deer (), and the red deer (). The study determined the levels of Cs-137 in muscle samples of these game animals in 2015-2022.
MATERIAL AND METHODS
Using gamma radiation spectrometry, 858 samples of game animal muscle tissue were examined: 508 wild boar, 145 roe deer and 205 red deer samples.
RESULTS
Concentrations of Cs-137 varied widely (from minimum detectable activity (MDA) values to over 4,000 Bq/kg). In 63.4% of cases, the obtained concentrations exceeded the MDA. The permissible limit (600 Bq/kg for food) was exceeded in nine wild boar muscle samples, whereas it was not even exceeded once in roe or red deer muscle. The average concentration in wild boar was three times higher than in roe and red deer and amounted to 42.84 Bq/kg. The highest concentration of Cs-137 in wild boar muscle was 4,195 ± 372.0 Bq/kg, in roe deer muscle it was 111.5 ± 12.50 Bq/kg, and in red deer muscle was 86.70 ± 3.470 Bq/kg.
CONCLUSION
The seven years' data indicate that wild boar absorb the most caesium-137 among game animals. The concentrations of Cs-137 in the muscle of game animals in the years 2015-2022 were at a nearly constant level, a very slow diminution being noticeable over time in roe and red deer muscle.
PubMed: 38947154
DOI: 10.2478/jvetres-2024-0026 -
Life Science Alliance Sep 2024This work presents a novel consensus molecular subtype (CMS) classifier for colorectal cancer (CRC), optimized for RNA-sequencing data stemming from degraded RNA of...
This work presents a novel consensus molecular subtype (CMS) classifier for colorectal cancer (CRC), optimized for RNA-sequencing data stemming from degraded RNA of clinical formalin-fixed paraffin-embedded (FFPE) tissue samples (the CMSFFPE classifier).
PubMed: 38936972
DOI: 10.26508/lsa.202402889 -
Journal of Personalized Medicine May 2024In reconstructive surgery, local flaps might develop tissue necrosis or partial flap loss especially after previous irradiation, which may be necessary in many tumor...
BACKGROUND
In reconstructive surgery, local flaps might develop tissue necrosis or partial flap loss especially after previous irradiation, which may be necessary in many tumor entities. The application of stem cells seems promising to improve flap perfusion and might be a possible solution to optimize flap survival.
METHODS
Twenty rats received harvesting of bilateral random pattern fasciocutaneous flaps. The right flaps received 20 Gy ionizing radiation 4 weeks prior to the surgery, while the left flaps served as the non-irradiated control. After flap harvest, four different stem cell mixtures (5 × 10 ASC, ASC-HUVEC, MSC, MSC-HUVEC) were applied under both right and left flaps using 1 mL fibrin glue as the delivery vehicle. Flap size and its necrotic area were examined clinically. Two weeks after the surgery, HE staining and immunohistochemical staining for CD68 and ERG, as well as PCR analysis (Interleukin 6, HIF-1α and VEGF), were performed.
RESULTS
Application of ASCs, ASCs-HUVECs and MSCs resulted in a lower number of CD68-stained cells compared to the no cell group. The expression of Hif1α was higher in the ASC group compared to those in the MSC and previously treated no cell groups. Treatment with MSCs and MSCs-HUVECs prevented shrinking of the flaps in this series.
CONCLUSION
Application of ASCs, MSCs and ASCs-HUVECs was shown to have an antiinflammatory effect. Treatment with MSCs and MSCs-HUVECs can prevent early shrinking of the flaps.
PubMed: 38929774
DOI: 10.3390/jpm14060554 -
Life (Basel, Switzerland) May 2024Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and is associated with high recurrence rates, a high incidence of distant metastases...
Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and is associated with high recurrence rates, a high incidence of distant metastases and poor overall survival. The aim of this study was to investigate the role of PD-L1, EGFR and AR expression in TNBC promotion and progression. To that end, we analyzed the immunohistochemical expression of these genes in 125 TNBC patients and their relation to clinicopathological parameters and survival. An elevated expression of PD-L1 was significantly correlated with higher tumor and nuclear grade, while a low expression was correlated with loco-regional recurrence without any influence on survival. Contrary to this, the expression of AR showed a positive impact on the DFI and a negative association with tumor grade. Furthermore, PD-L1 and AR demonstrated simultaneous expression, and further co-expression analysis revealed that a positive expression of PD-L1/AR notably correlates with tumor and nuclear grade and has a significant impact on a longer DFI and OS, while a negative PD-L1/AR expression is significantly associated with metastases. Therefore, our results suggest that positive PD-L1/AR expression is beneficial for TNBC patients. In addition, an elevated expression of EGFR contributes to metastases and a worse DFI and OS. In conclusion, we think that low PD-L1/low AR/high EGFR expression followed by high Ki67 expression constitutes a 'high risk' profile of TNBC.
PubMed: 38929666
DOI: 10.3390/life14060682 -
Brain Sciences Jun 2024Ageing is a continuous process that can cause neurodevelopmental changes in the body. Several studies have examined its effects, but few have focused on how time affects...
Ageing is a continuous process that can cause neurodevelopmental changes in the body. Several studies have examined its effects, but few have focused on how time affects biological processes in the early stages of brain development. As studying the changes that occur in the early stages of life is important to prevent age-related neurological and psychiatric disorders, we aim to focus on these changes. The transcriptomic markers of ageing that are common to the analysed brain regions of C57Bl/6J mice were identified after conducting two-way ANOVA tests and effect size analysis on the time courses of gene expression profiles in various mouse brain regions. A total of 16,374 genes (59.9%) significantly changed their expression level, among which 7600 (27.8%) demonstrated tissue-dependent differences only, and 1823 (6.7%) displayed time-dependent and tissue-independent responses. Focusing on genes with at least a large effect size gives the list of potential biomarkers 12,332 (45.1%) and 1670 (6.1%) genes, respectively. There were 305 genes that exhibited similar significant time response trends (independently of the brain region). Samples from an 11-day-old mouse embryo validated the identified early-stage brain ageing markers. The overall functional analysis revealed tRNA and rRNA processing in the mitochondrion and contact activation system (CAS), as well as the kallikrein/kinin system (KKS), together with clotting cascade and defective factor F9 activation being affected by ageing. Most ageing-related pathways were significantly enriched, especially those that are strongly connected to development processes and neurodegenerative diseases.
PubMed: 38928581
DOI: 10.3390/brainsci14060581 -
International Journal of Molecular... Jun 2024Hypoxia-inducible factor 1-alpha (HIF1A) is a key transcription factor aiding tumor cells' adaptation to hypoxia, regulated by the prolyl hydroxylase family (EGLN1-3) by...
Hypoxia-inducible factor 1-alpha (HIF1A) is a key transcription factor aiding tumor cells' adaptation to hypoxia, regulated by the prolyl hydroxylase family (EGLN1-3) by directing toward degradation pathways. DNA methylation potentially influences EGLN and HIF1A levels, impacting cellular responses to hypoxia. We examined 96 HNSCC patients and three cell lines, analyzing gene expression of , , , , and at the mRNA level and EGLN1 protein levels. Methylation levels of and were assessed through high-resolution melting analysis. Bioinformatics tools were employed to characterize associations between and expression and methylation. We found significantly higher mRNA levels of , , , , and ( = 0.021; < 0.0001; < 0.0001; = 0.004, and < 0.0001, respectively) genes in tumor tissues compared to normal ones and downregulation of the mRNA level in tumor tissues ( = 0.0013). In HNSCC patients with hypermethylation of in normal tissue, we noted a reduction in mRNA levels compared to tumor tissue ( = 0.04). In conclusion, the differential expression of and genes in HNSCC tumors compared to normal tissues influences patients' overall survival, highlighting their role in tumor development. Moreover, DNA methylation could be responsible for suppression in the normal tissues of HNSCC patients.
Topics: Humans; DNA Methylation; Hypoxia-Inducible Factor 1, alpha Subunit; Squamous Cell Carcinoma of Head and Neck; Female; Head and Neck Neoplasms; Male; Gene Expression Regulation, Neoplastic; Cell Line, Tumor; Hypoxia-Inducible Factor-Proline Dioxygenases; Middle Aged; Prolyl Hydroxylases; Aged; Carcinogenesis; Adult
PubMed: 38928200
DOI: 10.3390/ijms25126495 -
Healthcare (Basel, Switzerland) Jun 2024We compared the managing of prevention methods for SARS-CoV-2 infections in dental offices before and immediately after the COVID-19 pandemic. The purpose of this study...
We compared the managing of prevention methods for SARS-CoV-2 infections in dental offices before and immediately after the COVID-19 pandemic. The purpose of this study was to find out the varieties of infection prevention methods used by dentists before and during the pandemic and compare them. We designed a digital transversal questionnaire with 15 closed questions that was sent to 150 dentists in Bucharest, Romania. We received = 112 valid answers during July-August 2021 from dentists of all age groups (25-60 years), with a sex ratio of 0.36, which agreed to anonymously participate in this study. The results showed an increase in types and amount of personal protection equipment (i.e., ocular/facial protection, supplemental gown, and upgrading the FFP1 masks to FFP2 or FFP3). Ocular protection showed statistical significance by gender but not by age group. Vaccination rate against SARS-CoV-2 was at 80% of the participant dentists at the time of the survey and had statistical significance. However, vaccination status of the patients did not alter dentists' protection protocol.
PubMed: 38921284
DOI: 10.3390/healthcare12121169 -
Cells Jun 2024The use of charged particle radiotherapy is currently increasing, but combination therapy with DNA repair inhibitors remains to be exploited in the clinic. The... (Review)
Review
The use of charged particle radiotherapy is currently increasing, but combination therapy with DNA repair inhibitors remains to be exploited in the clinic. The high-linear energy transfer (LET) radiation delivered by charged particles causes clustered DNA damage, which is particularly effective in destroying cancer cells. Whether the DNA damage response to this type of damage is different from that elicited in response to low-LET radiation, and if and how it can be targeted to increase treatment efficacy, is not fully understood. Although several preclinical studies have reported radiosensitizing effects when proton or carbon ion irradiation is combined with inhibitors of, e.g., PARP, ATR, ATM, or DNA-PKcs, further exploration is required to determine the most effective treatments. Here, we examine what is known about repair pathway choice in response to high- versus low-LET irradiation, and we discuss the effects of inhibitors of these pathways when combined with protons and carbon ions. Additionally, we explore the potential effects of DNA repair inhibitors on antitumor immune signaling upon proton and carbon ion irradiation. Due to the reduced effect on healthy tissue and better immune preservation, particle therapy may be particularly well suited for combination with DNA repair inhibitors.
Topics: Humans; DNA Repair; DNA Damage; Proton Therapy; Heavy Ion Radiotherapy; Neoplasms; Animals; Linear Energy Transfer
PubMed: 38920686
DOI: 10.3390/cells13121058