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Plant Biology (Stuttgart, Germany) Jun 2024In Mediterranean regions, severe summers are becoming more common, leading to restrictions to vine productivity and yield quality, requiring sustainable practices to...
In Mediterranean regions, severe summers are becoming more common, leading to restrictions to vine productivity and yield quality, requiring sustainable practices to support this sector. We assessed the behaviour of three red grapevine varieties from the Douro Region to examine their tolerance to summer climate stress from the perspective that the less common varieties may have potential for increased use in a climate change scenario. Leaf and fruit biochemical profile, antioxidant activity and fruit colorimetric parameters were assessed at different phenological stages in Aragonez (AR), Tinto Cão (TC) and Touriga Nacional (TN) grape varieties. All three varieties exhibit significant variability in phenological timing, influenced by genetic and environmental factors. Photosynthetic pigment strategies differed among varieties. Chlorophyll content in AR was high to cope with high radiation, while TN displaying a balanced approach, and TC had lower pigment levels, with higher levels of phenolics, antioxidants, and soluble sugars, particularly during stress. The variations in berry biochemical profile highlight the distinct characteristics of the varieties. TC and TN show potential for coping with climate change, having elevated total acidity, while AR has larger and heavier berries with distinct coloration. These findings reinforce the need to study the behaviour of different varieties in each Terroir, to understand their diverse strategies to deal with summer climate stress. This will help in selecting the most suitable variety for these conditions under vineyard management in the Douro Region.
PubMed: 38886872
DOI: 10.1111/plb.13671 -
Radiation Oncology (London, England) Jun 2024Rare but severe toxicities of the optic apparatus have been observed after treatment of intracranial tumours with proton therapy. Some adverse events have occurred at...
BACKGROUND AND PURPOSE
Rare but severe toxicities of the optic apparatus have been observed after treatment of intracranial tumours with proton therapy. Some adverse events have occurred at unusually low dose levels and are thus difficult to understand considering dose metrics only. When transitioning from double scattering to pencil beam scanning, little consideration was given to increased dose rates observed with the latter delivery paradigm. We explored if dose rate related metrics could provide additional predicting factors for the development of late visual toxicities.
MATERIALS AND METHODS
Radiation-induced intracranial visual pathway lesions were delineated on MRI for all index cases. Voxel-wise maximum dose rate (MDR) was calculated for 2 patients with observed optic nerve toxicities (CTCAE grade 3 and 4), and 6 similar control cases. Additionally, linear energy transfer (LET) related dose enhancing metrics were investigated.
RESULTS
For the index cases, which developed toxicities at low dose levels (mean, 50 Gy), some dose was delivered at higher instantaneous dose rates. While optic structures of non-toxicity cases were exposed to dose rates of up to 1 to 3.2 Gy/s, the pre-chiasmatic optic nerves of the 2 toxicity cases were exposed to dose rates above 3.7 Gy/s. LET-related metrics were not substantially different between the index and non-toxicity cases.
CONCLUSIONS
Our observations reveal large variations in instantaneous dose rates experienced by different volumes within our patient cohort, even when considering the same indications and beam arrangement. High dose rate regions are spatially overlapping with the radiation induced toxicity areas in the follow up images. At this point, it is not feasible to establish causality between exposure to high dose rates and the development of late optic apparatus toxicities due to the low incidence of injury.
Topics: Humans; Proton Therapy; Brain Neoplasms; Radiotherapy Dosage; Female; Male; Middle Aged; Adult; Radiation Injuries; Aged; Optic Nerve; Organs at Risk; Radiotherapy Planning, Computer-Assisted; Dose-Response Relationship, Radiation
PubMed: 38886727
DOI: 10.1186/s13014-024-02464-z -
Molecular Pharmaceutics Jul 2024Squamous cell carcinoma (SCC) is a common nonmelanoma skin cancer. Radiotherapy plays an integral role in treating SCC due to its characteristics, such as diminished...
Squamous cell carcinoma (SCC) is a common nonmelanoma skin cancer. Radiotherapy plays an integral role in treating SCC due to its characteristics, such as diminished intercellular adhesion, heightened cell migration and invasion capabilities, and immune evasion. These problems lead to inaccurate tumor boundary positioning and radiotherapy tolerance in SCC treatment. Thus, accurate localization and enhanced radiotherapy sensitivity are imperative for effective SCC treatment. To address the existing limitations in SCC therapy, we developed monoglyceride solid lipid nanoparticles (MG SLNs) and enveloped them with the A431 cell membrane (A431 CM) to create A431@MG. The characterization results showed that A431@MG was spherical. Furthermore, A431@MG had specific targeting for A431 cells. In A431 tumor-bearing mice, A431@MG demonstrated prolonged accumulation within tumors, ensuring precise boundary localization of SCC. We further advanced the approach by preparing MG SLNs encapsulating 5-aminolevulinic acid methyl ester (MLA) and desferrioxamine (DFO) with an A431 CM coating to yield A431@MG-MLA/DFO. Several studies have revealed that DFO effectively reduced iron content, impeding protoporphyrin IX (PpIX) biotransformation and promoting PpIX accumulation. Simultaneously, MLA was metabolized into PpIX upon cellular entry. During radiotherapy, the heightened PpIX levels enhanced reactive oxygen species (ROS) generation, inducing DNA and mitochondrial damage and leading to cell apoptosis. In A431 tumor-bearing mice, the A431@MG-MLA/DFO group exhibited notable radiotherapy sensitization, displaying superior tumor growth inhibition. Combining A431@MG-MLA/DFO with radiotherapy significantly improved anticancer efficacy, highlighting its potential to serve as an integrated diagnostic and therapeutic strategy for SCC.
Topics: Animals; Mice; Nanoparticles; Humans; Cell Line, Tumor; Skin Neoplasms; Carcinoma, Squamous Cell; Radiation-Sensitizing Agents; Cell Membrane; Aminolevulinic Acid; Lipids; Xenograft Model Antitumor Assays; Deferoxamine; Mice, Nude; Female; Mice, Inbred BALB C; Reactive Oxygen Species; Apoptosis; Liposomes
PubMed: 38885477
DOI: 10.1021/acs.molpharmaceut.3c01247 -
Clinical and Experimental Medicine Jun 2024CD8 + T cells exert a critical role in eliminating cancers and chronic infections, and can provide long-term protective immunity. However, under the exposure of... (Review)
Review
CD8 + T cells exert a critical role in eliminating cancers and chronic infections, and can provide long-term protective immunity. However, under the exposure of persistent antigen, CD8 + T cells can differentiate into terminally exhausted CD8 + T cells and lose the ability of immune surveillance and disease clearance. New insights into the molecular mechanisms of T-cell exhaustion suggest that it is a potential way to improve the efficacy of immunotherapy by restoring the function of exhausted CD8 + T cells. Transforming growth factor-β (TGF-β) is an important executor of immune homeostasis and tolerance, inhibiting the expansion and function of many components of the immune system. Recent studies have shown that TGF-β is one of the drivers for the development of exhausted CD8 + T cells. In this review, we summarized the role and mechanisms of TGF-β in the formation of exhausted CD8 + T cells and discussed ways to target those to ultimately enhance the efficacy of immunotherapy.
Topics: Humans; Transforming Growth Factor beta; CD8-Positive T-Lymphocytes; Immunotherapy; Neoplasms; Animals
PubMed: 38884843
DOI: 10.1007/s10238-024-01394-0 -
Physical and Engineering Sciences in... Jun 2024The volumetric reduction rate (VRR) was evaluated with consideration for six degrees-of-freedom (6DoF) patient setup errors based on a mathematical tumor model in...
Assessing tumor volumetric reduction with consideration for setup errors based on mathematical tumor model and microdosimetric kinetic model in single-isocenter VMAT for brain metastases.
The volumetric reduction rate (VRR) was evaluated with consideration for six degrees-of-freedom (6DoF) patient setup errors based on a mathematical tumor model in single-isocenter volumetric modulated arc therapy (SI-VMAT) for brain metastases. Simulated gross tumor volumes (GTV) of 1.0 cm and dose distribution were created (27 Gy/3 fractions). The distance between the GTV center and isocenter (d) was set at 0-10 cm. The GTV was translated within 0-1.0 mm (Trans) and rotated within 0-1.0° (Rot) in the three axis directions using affine transformation. The tumor growth volume was calculated using a multicomponent mathematical model (MCTM), and lethal effects of irradiation and repair from damage during irradiation were calculated by a microdosimetric kinetic model (MKM) for non-small cell lung cancer (NSCLC) A549 and NCI-H460 (H460) cells. The VRRs were calculated 5 days after the end of irradiation using the physical dose to the GTV for varying d and 6DoF setup errors. The tolerance value of VRR, the GTV volume reduction rate, was set at 5%, based on the pre-irradiation GTV volume. With the exception of the only one A549 condition where (Trans, Rot) = (1.0 mm, 1.0°) was repeated for 3 fractions, all conditions met all the tolerance VRR values for A549 and H460 cells with varying d from 0 to 10 cm. Evaluation based on the mathematical tumor model suggested that if the 6DoF setup errors at each irradiation could be kept within 1.0 mm and 1.0°, there would be little effect on tumor volume regardless of the distance from the isocenter in SI-VMAT.
PubMed: 38884671
DOI: 10.1007/s13246-024-01451-8 -
Clinical and Translational Radiation... Jul 2024Aim of the present study is to characterize a deep learning-based auto-segmentation software (DL) for prostate cone beam computed tomography (CBCT) images and to...
PURPOSE
Aim of the present study is to characterize a deep learning-based auto-segmentation software (DL) for prostate cone beam computed tomography (CBCT) images and to evaluate its applicability in clinical adaptive radiation therapy routine.
MATERIALS AND METHODS
Ten patients, who received exclusive radiation therapy with definitive intent on the prostate gland and seminal vesicles, were selected. Femoral heads, bladder, rectum, prostate, and seminal vesicles were retrospectively contoured by four different expert radiation oncologists on patients CBCT, acquired during treatment. Consensus contours (CC) were generated starting from these data and compared with those created by DL with different algorithms, trained on CBCT (DL-CBCT) or computed tomography (DL-CT). Dice similarity coefficient (DSC), centre of mass (COM) shift and volume relative variation (VRV) were chosen as comparison metrics. Since no tolerance limit can be defined, results were also compared with the inter-operator variability (IOV), using the same metrics.
RESULTS
The best agreement between DL and CC was observed for femoral heads (DSC of 0.96 for both DL-CBCT and DL-CT). Performance worsened for low-contrast soft tissue organs: the worst results were found for seminal vesicles (DSC of 0.70 and 0.59 for DL-CBCT and DL-CT, respectively). The analysis shows that it is appropriate to use algorithms trained on the specific imaging modality. Furthermore, the statistical analysis showed that, for almost all considered structures, there is no significant difference between DL-CBCT and human operator in terms of IOV.
CONCLUSIONS
The accuracy of DL-CBCT is in accordance with CC; its use in clinical practice is justified by the comparison with the inter-operator variability.
PubMed: 38884004
DOI: 10.1016/j.ctro.2024.100796 -
Frontiers in Plant Science 2024Plantations located outside the species distribution area represent natural experiments to assess tree tolerance to climate variability. Climate change amplifies...
INTRODUCTION
Plantations located outside the species distribution area represent natural experiments to assess tree tolerance to climate variability. Climate change amplifies warming-related drought stress but also leads to more climate extremes.
METHODS
We studied plantations of the European larch (Larix decidua), a conifer native to central and eastern Europe, in northern Spain. We used climate, drought and tree-ring data from four larch plantations including wet (Valgañón, site V; Santurde, site S), intermediate (Ribavellosa, site R) and dry (Santa Marina, site M) sites. We aimed to benchmark the larch tolerance to climate and drought stress by analysing the relationships between radial growth increment (hereafter growth), climate data (temperature, precipitation, radiation) and a drought index.
RESULTS
Basal area increment (BAI) was the lowest in the driest site M (5.2 cm2 yr-1; period 1988-2022), followed by site R (7.5 cm2 yr-1), with the youngest and oldest and trees being planted in M (35 years) and R (150 years) sites. BAI peaked in the wettest sites (V; 10.4 cm2 yr-1; S, 10.8 cm2 yr-1). We detected a sharp BAI reduction (30% of the regional mean) in 2001 when springto-summer conditions were very dry. In the wettest V and S sites, larch growth positively responded to current March and June-July radiation, but negatively to March precipitation. In the R site, high April precipitation enhanced growth. In the driest M site, warm conditions in the late prior winter and current spring improved growth, but warm-sunny conditions in July and dry-sunny conditions in August reduced it. Larch growth positively responded to spring-summer wet conditions considering short (1-6 months) and long (9-24 months) time scales in dry (site M) and wet-intermediate (sites S and R) sites, respectively.
DISCUSSION
Larch growth is vulnerable to drought stress in dry slow-growing plantations, but also to extreme spring wet-cloudy events followed by dry-hot conditions in wet fast-growing plantations.
PubMed: 38882570
DOI: 10.3389/fpls.2024.1404347 -
The Journal of Heredity Jun 2024Strong gene flow from outcrossing relatives tends to blur species boundaries, while divergent ecological selection can counteract gene flow. To better understand how...
Strong gene flow from outcrossing relatives tends to blur species boundaries, while divergent ecological selection can counteract gene flow. To better understand how these two forces affect the maintenance of species boundaries, we focused on a species complex including a rare species, maple-leaf oak (Quercus acerifolia), which is found in only four disjunct ridges in Arkansas. Its limited range and geographic proximity to co-occurring close relatives create the possibility for genetic swamping. In this study, we gathered genome-wide SNPs using restriction-site associated DNA sequencing (RADseq) from 190 samples of Q. acerifolia and three of its close relatives, Q. shumardii, Q. buckleyi, and Q. rubra. We found that Q. shumardii and Q. acerifolia are reciprocally monophyletic with low support, suggesting incomplete lineage sorting, introgression between Q. shumardii and Q. acerifolia, or both. Analyses that model allele distributions demonstrate that admixture contributes strongly to this pattern. Populations of Q. acerifolia experience gene flow from Q. shumardii and Q. rubra, but we found evidence that divergent selection is likely maintaining species boundaries: 1) ex situ collections of Q. acerifolia have a higher proportion of hybrids compared to the mature trees of the wild populations, suggesting ecological selection against hybrids at the seed/seedling stage; 2) ecological traits co-vary with genomic composition; and 3) Q. acerifolia shows genetic differentiation at loci hypothesized to influence tolerance of radiation, drought, and high temperature. Our findings strongly suggest that in maple-leaf oak, selection results in higher divergence at regions of the genome despite gene flow from close relatives.
PubMed: 38881254
DOI: 10.1093/jhered/esae033 -
Seminars in Radiation Oncology Jul 2024Treating radioresistant and bulky tumors is challenging due to their inherent resistance to standard therapies and their large size. GRID and lattice spatially... (Review)
Review
Treating radioresistant and bulky tumors is challenging due to their inherent resistance to standard therapies and their large size. GRID and lattice spatially fractionated radiation therapy (simply referred to GRID RT and LRT) offer promising techniques to tackle these issues. Both approaches deliver radiation in a grid-like or lattice pattern, creating high-dose peaks surrounded by low-dose valleys. This pattern enables the destruction of significant portions of the tumor while sparing healthy tissue. GRID RT uses a 2-dimensional pattern of high-dose peaks (15-20 Gy), while LRT delivers a three-dimensional array of high-dose vertices (10-20 Gy) spaced 2-5 cm apart. These techniques are beneficial for treating a variety of cancers, including soft tissue sarcomas, osteosarcomas, renal cell carcinoma, melanoma, gastrointestinal stromal tumors (GISTs), pancreatic cancer, glioblastoma, and hepatocellular carcinoma. The specific grid and lattice patterns must be carefully tailored for each cancer type to maximize the peak-to-valley dose ratio while protecting critical organs and minimizing collateral damage. For gynecologic cancers, the treatment plan should align with the international consensus guidelines, incorporating concurrent chemotherapy for optimal outcomes. Despite the challenges of precise dosimetry and patient selection, GRID RT and LRT can be cost-effective using existing radiation equipment, including particle therapy systems, to deliver targeted high-dose radiation peaks. This phased approach of partial high-dose induction radiation therapy with standard fractionated radiation therapy maximizes immune modulation and tumor control while reducing toxicity. Comprehensive treatment plans using these advanced techniques offer a valuable framework for radiation oncologists, ensuring safe and effective delivery of therapy for radioresistant and bulky tumors. Further clinical trials data and standardized guidelines will refine these strategies, helping expand access to innovative cancer treatments.
Topics: Humans; Neoplasms; Dose Fractionation, Radiation; Radiation Tolerance; Radiotherapy Planning, Computer-Assisted
PubMed: 38880540
DOI: 10.1016/j.semradonc.2024.05.002 -
Seminars in Radiation Oncology Jul 2024Radiotherapy elicits dose- and lineage-dependent effects on immune cell survival, migration, activation, and proliferation in targeted tumor microenvironments. Radiation... (Review)
Review
Radiotherapy elicits dose- and lineage-dependent effects on immune cell survival, migration, activation, and proliferation in targeted tumor microenvironments. Radiation also stimulates phenotypic changes that modulate the immune susceptibility of tumor cells. This has raised interest in using radiotherapy to promote greater response to immunotherapies. To clarify the potential of such combinations, it is critical to understand how best to administer radiation therapy to achieve activation of desired immunologic mechanisms. In considering the multifaceted process of priming and propagating anti-tumor immune response, radiation dose heterogeneity emerges as a potential means for simultaneously engaging diverse dose-dependent effects in a single tumor environment. Recent work in spatially fractionated external beam radiation therapy demonstrates the expansive immune responses achievable when a range of high to low dose radiation is delivered in a tumor. Brachytherapy and radiopharmaceutical therapies deliver inherently heterogeneous distributions of radiation that may contribute to immunogenicity. This review evaluates the interplay of radiation dose and anti-tumor immune response and explores emerging methodological approaches for investigating the effects of heterogeneous dose distribution on immune responses.
Topics: Humans; Tumor Microenvironment; Neoplasms; Radiotherapy Dosage; Immunotherapy; Dose-Response Relationship, Radiation; Animals
PubMed: 38880534
DOI: 10.1016/j.semradonc.2024.04.004