-
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 -
Frontiers in Oncology 2024We tried to establish the normal tissue complication probability (NTCP) model of temporal lobe injury of recurrent nasopharyngeal carcinoma (NPC) patients after two...
PURPOSE
We tried to establish the normal tissue complication probability (NTCP) model of temporal lobe injury of recurrent nasopharyngeal carcinoma (NPC) patients after two courses of intensity modulated radiotherapy (IMRT) to provide more reliable dose-volume data reference to set the temporal lobe tolerance dose for recurrent NPC patients in the future.
METHODS AND MATERIALS
Recurrent NPC patients were randomly divided into training data set and validation data set in a ratio of 2:1, All the temporal lobes (TLs) were re-contoured as R/L structures and named separately in the MIM system. The dose distribution of the initial IMRT plan was deformed into the second course planning CT via MIM software to get the deformed dose. Equivalent dose of TLs in 2Gy fractions was calculated via linear quadratic model, using an α/β=3 for temporal lobes. NTCP model that correlated the irradiated volume of the temporal lobe and? the clinical variables were evaluated in a multivariate prediction model using AUC analysis.
RESULTS
From Jan. 2010 to Dec. 2020, 78 patients were enrolled into our study. Among which 26 (33.3%) developed TLI. The most important factors affecting TLI was the sum-dose d1.5cc of TL, while the possible clinical factors did not reach statistically significant differences in multivariate analysis. According to NTCP model, the TD5 and TD50 EQD2 dose of sum-dose d1.5cc were 65.26Gy (46.72-80.69Gy) and 125.25Gy (89.51-152.18Gy), respectively. For the accumulated EQD2 dose, the area under ROC shadow was 0.8702 (0.7577-0.9828) in model validation, p<0.001.
CONCLUSION
In this study, a NTCP model of temporal lobe injury after a second course of IMRT for recurrent nasopharyngeal carcinoma was established. TD5 and TD50 doses of temporal lobe injury after re-RT were obtained according to the model, and the model was verified by validation set data.
PubMed: 38873258
DOI: 10.3389/fonc.2024.1394111 -
Nature Communications Jun 2024Genetic testing is crucial for precision cancer medicine. However, detecting multiple same-site insertions or deletions (indels) is challenging. Here, we introduce CoHIT...
Genetic testing is crucial for precision cancer medicine. However, detecting multiple same-site insertions or deletions (indels) is challenging. Here, we introduce CoHIT (Cas12a-based One-for-all High-speed Isothermal Test), a one-pot CRISPR-based assay for indel detection. Leveraging an engineered AsCas12a protein variant with high mismatch tolerance and broad PAM scope, CoHIT can use a single crRNA to detect multiple NPM1 gene c.863_864 4-bp insertions in acute myeloid leukemia (AML). After optimizing multiple parameters, CoHIT achieves a detection limit of 0.01% and rapid results within 30 minutes, without wild-type cross-reactivity. It successfully identifies NPM1 mutations in 30 out of 108 AML patients and demonstrates potential in monitoring minimal residual disease (MRD) through continuous sample analysis from three patients. The CoHIT method is also competent for detecting indels of KIT, BRAF, and EGFR genes. Integration with lateral flow test strips and microfluidic chips highlights CoHIT's adaptability and multiplexing capability, promising significant advancements in clinical cancer diagnostics.
Topics: Humans; Leukemia, Myeloid, Acute; INDEL Mutation; CRISPR-Cas Systems; Nucleophosmin; Neoplasm, Residual; Nuclear Proteins; Proto-Oncogene Proteins B-raf; Genetic Testing; ErbB Receptors; Bacterial Proteins; Endodeoxyribonucleases; CRISPR-Associated Proteins
PubMed: 38866774
DOI: 10.1038/s41467-024-49414-7 -
Journal of Experimental & Clinical... Jun 2024Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer subtype often treated with radiotherapy (RT). Due to its intrinsic heterogeneity and...
BACKGROUND
Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer subtype often treated with radiotherapy (RT). Due to its intrinsic heterogeneity and lack of effective targets, it is crucial to identify novel molecular targets that would increase RT efficacy. Here we demonstrate the role of BUB1 (cell cycle Ser/Thr kinase) in TNBC radioresistance and offer a novel strategy to improve TNBC treatment.
METHODS
Gene expression analysis was performed to look at genes upregulated in TNBC patient samples compared to other subtypes. Cell proliferation and clonogenic survivals assays determined the IC of BUB1 inhibitor (BAY1816032) and radiation enhancement ratio (rER) with pharmacologic and genomic BUB1 inhibition. Mammary fat pad xenografts experiments were performed in CB17/SCID. The mechanism through which BUB1 inhibitor sensitizes TNBC cells to radiotherapy was delineated by γ-H2AX foci assays, BLRR, Immunoblotting, qPCR, CHX chase, and cell fractionation assays.
RESULTS
BUB1 is overexpressed in BC and its expression is considerably elevated in TNBC with poor survival outcomes. Pharmacological or genomic ablation of BUB1 sensitized multiple TNBC cell lines to cell killing by radiation, although breast epithelial cells showed no radiosensitization with BUB1 inhibition. Kinase function of BUB1 is mainly accountable for this radiosensitization phenotype. BUB1 ablation also led to radiosensitization in TNBC tumor xenografts with significantly increased tumor growth delay and overall survival. Mechanistically, BUB1 ablation inhibited the repair of radiation-induced DNA double strand breaks (DSBs). BUB1 ablation stabilized phospho-DNAPKcs (S2056) following RT such that half-lives could not be estimated. In contrast, RT alone caused BUB1 stabilization, but pre-treatment with BUB1 inhibitor prevented stabilization (t, ~8 h). Nuclear and chromatin-enriched fractionations illustrated an increase in recruitment of phospho- and total-DNAPK, and KAP1 to chromatin indicating that BUB1 is indispensable in the activation and recruitment of non-homologous end joining (NHEJ) proteins to DSBs. Additionally, BUB1 staining of TNBC tissue microarrays demonstrated significant correlation of BUB1 protein expression with tumor grade.
CONCLUSIONS
BUB1 ablation sensitizes TNBC cell lines and xenografts to RT and BUB1 mediated radiosensitization may occur through NHEJ. Together, these results highlight BUB1 as a novel molecular target for radiosensitization in women with TNBC.
Topics: Humans; Triple Negative Breast Neoplasms; Animals; Female; Mice; Radiation Tolerance; Cell Line, Tumor; DNA End-Joining Repair; Protein Serine-Threonine Kinases; Xenograft Model Antitumor Assays; Cell Proliferation; Gene Expression Regulation, Neoplastic; Mice, SCID
PubMed: 38863037
DOI: 10.1186/s13046-024-03086-9 -
Radiotherapy and Oncology : Journal of... Jun 2024Use of stereotactic ablative radiotherapy (SABR) for central lung tumors can result in up to a 35% incidence of late pulmonary toxicity. We evaluated an automated...
INTRODUCTION
Use of stereotactic ablative radiotherapy (SABR) for central lung tumors can result in up to a 35% incidence of late pulmonary toxicity. We evaluated an automated scoring method to quantify post-SABR bronchial changes by using artificial intelligence (AI)-based airway segmentation.
MATERIALS AND METHODS
Central lung SABR patients treated at Amsterdam UMC (AUMC, internal reference dataset) and Peter MacCallum Cancer Centre (PMCC, external validation dataset) were identified. Patients were eligible if they had pre- and post-SABR CT scans with ≤ 1 mm slice thickness. The first step of the automated scoring method involved AI-based airway auto-segmentation using MEDPSeg, an end-to-end deep learning-based model. The Vascular Modeling Toolkit in 3D Slicer was then used to extract a centerline curve through the auto-segmented airway lumen, and cross-sectional measurements were computed along each bronchus for all CT scans. For AUMC patients, airway stenosis/occlusion was evaluated by both visual assessment and automated scoring. Only the automated method was applied to the PMCC dataset.
RESULTS
Study patients comprised 26 from AUMC, and 33 from PMCC. Visual scoring identified stenosis/occlusion in 8 AUMC patients (31 %), most frequently in the segmental bronchi. After airway auto-segmentation, minor manual edits were needed in 9 % of patients. Segmentation for a single scan averaged 83sec (range 73-136). Automated scoring nearly doubled detected airway stenosis/occlusion (n = 15, 58 %), and allowed for earlier detection in 5/8 patients who had also visually scored changes. Estimated rates were 48 % and 66 % at 1- and 2-years, respectively, for the internal dataset. The automated detection rate was 52 % in the external dataset, with 1- and 2-year risks of 56 % and 61 %, respectively.
CONCLUSION
An AI-based automated scoring method allows for detection of more bronchial stenosis/occlusion after lung SABR, and at an earlier time-point. This tool can facilitate studies to determine early airway changes and establish more reliable airway tolerance doses.
PubMed: 38857700
DOI: 10.1016/j.radonc.2024.110376 -
PloS One 2024This paper reports the results of gamma irradiation experiments and whole genome sequencing (WGS) performed on vegetative cells of two radiation resistant bacterial...
This paper reports the results of gamma irradiation experiments and whole genome sequencing (WGS) performed on vegetative cells of two radiation resistant bacterial strains, Metabacillus halosaccharovorans (VITHBRA001) and Bacillus paralicheniformis (VITHBRA024) (D10 values 2.32 kGy and 1.42 kGy, respectively), inhabiting the top-ranking high background radiation area (HBRA) of Chavara-Neendakara placer deposit (Kerala, India). The present investigation has been carried out in the context that information on strategies of bacteria having mid-range resistance for gamma radiation is inadequate. WGS, annotation, COG and KEGG analyses and manual curation of genes helped us address the possible pathways involved in the major domains of radiation resistance, involving recombination repair, base excision repair, nucleotide excision repair and mismatch repair, and the antioxidant genes, which the candidate could activate to survive under ionizing radiation. Additionally, with the help of these data, we could compare the candidate strains with that of the extremely radiation resistant model bacterium Deinococccus radiodurans, so as to find the commonalities existing in their strategies of resistance on the one hand, and also the rationale behind the difference in D10, on the other. Genomic analysis of VITHBRA001 and VITHBRA024 has further helped us ascertain the difference in capability of radiation resistance between the two strains. Significantly, the genes such as uvsE (NER), frnE (protein protection), ppk1 and ppx (non-enzymatic metabolite production) and those for carotenoid biosynthesis, are endogenous to VITHBRA001, but absent in VITHBRA024, which could explain the former's better radiation resistance. Further, this is the first-time study performed on any bacterial population inhabiting an HBRA. This study also brings forward the two species whose radiation resistance has not been reported thus far, and add to the knowledge on radiation resistant capabilities of the phylum Firmicutes which are abundantly observed in extreme environment.
Topics: Radiation Tolerance; Genome, Bacterial; Gamma Rays; Background Radiation; Whole Genome Sequencing; India; Bacillus; DNA Repair
PubMed: 38857267
DOI: 10.1371/journal.pone.0304810 -
Frontiers in Pharmacology 2024Alternol is a natural compound isolated from the fermentation of a mutated fungus. We have demonstrated its potent anti-cancer effect the accumulation of radical oxygen...
INTRODUCTION
Alternol is a natural compound isolated from the fermentation of a mutated fungus. We have demonstrated its potent anti-cancer effect the accumulation of radical oxygen species (ROS) in prostate cancer cells and . In this study, we tested its anti-cancer spectrum in multiple platforms.
METHODS
We first tested its anti-cancer spectrum using the National Cancer Institute-60 (NCI-60) screening, a protein quantitation-based assay. CellTiter-Glo screening was utilized for ovarian cancer cell lines. Cell cycle distribution was analyzed using flow cytometry. Xenograft models in nude mice were used to assess anti-cancer effect. Healthy mice were tested for the acuate systemic toxicity.
RESULTS
Our results showed that Alternol exerted a potent anti-cancer effect on 50 (83%) cancer cell lines with a GI less than 5 µM and induced a lethal response in 12 (24%) of those 50 responding cell lines at 10 µM concentration. Consistently, Alternol displayed a similar anti-cancer effect on 14 ovarian cancer cell lines in an ATP quantitation-based assay. Most interestingly, Alternol showed an excellent safety profile with a maximum tolerance dose (MTD) at 665 mg/kg bodyweight in mice. Its therapeutic index was calculated as 13.3 based on the effective tumor-suppressing doses from HeLa and PC-3 cell-derived xenograft models.
CONCLUSION
Taken together, Alternol has a broad anti-cancer spectrum with a safe therapeutic index .
PubMed: 38855749
DOI: 10.3389/fphar.2024.1409506 -
BMC Cancer Jun 2024This study aimed to establish the dose-response relationship between volume base dose and tumor local control for vaginal cancer, including primary vaginal cancer and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study aimed to establish the dose-response relationship between volume base dose and tumor local control for vaginal cancer, including primary vaginal cancer and recurrent gynecologic malignancies in the vagina.
MATERIALS AND METHODS
We identified studies that reported volume base dose and local control by searching the PubMed, the Web of Science, and the Cochrane Library Database through August 12, 2023. The regression analyses were performed using probit model between volume based dose versus clinical outcomes. Subgroup analyses were performed according to stratification: publication year, country, inclusion time of patients, patients with prior radiotherapy, age, primaries or recurrent, tumor size, concurrent chemoradiotherapy proportion, dose rate, image modality for planning, and interstitial proportion.
RESULTS
A total of 879 patients with vaginal cancer were identified from 18 studies. Among them, 293 cases were primary vaginal cancer, 573 cases were recurrent cancer in the vagina, and 13 cases were unknown. The probit model showed a significant relationship between the HR-CTV (or CTV) D90 versus the 2-year and 3-year local control, P values were 0.013 and 0.014, respectively. The D90 corresponding to probabilities of 90% 2-year local control were 79.0 Gy (95% CI: 75.3-96.6 Gy).
CONCLUSIONS
A significant dependence of 2-year or 3-year local control on HR-CTV (or CTV) D90 was found. Our research findings encourage further validation of the dose-response relationship of radical radiotherapy for vaginal cancer through protocol based multicenter clinical trials.
Topics: Humans; Female; Vaginal Neoplasms; Dose-Response Relationship, Radiation; Radiotherapy Dosage; Neoplasm Recurrence, Local; Middle Aged; Treatment Outcome; Aged; Vagina
PubMed: 38851692
DOI: 10.1186/s12885-024-12486-1 -
Radiation Oncology (London, England) Jun 2024Particle therapy makes a noteworthy contribution in the treatment of tumor diseases. In order to be able to irradiate from different angles, usually expensive, complex...
BACKGROUND
Particle therapy makes a noteworthy contribution in the treatment of tumor diseases. In order to be able to irradiate from different angles, usually expensive, complex and large gantries are used. Instead rotating the beam via a gantry, the patient itself might be rotated. Here we present tolerance and compliance of volunteers for a fully-enclosed patient rotation system in a clinical magnetic resonance (MR)-scanner for potential use in MR-guided radiotherapy, conducted within a prospective evaluation study.
METHODS
A patient rotation system was used to simulate and perform magnetic resonance imaging (MRI)-examinations with 50 volunteers without an oncological question. For 20 participants, the MR-examination within the bore was simulated by introducing realistic MRI noise, whereas 30 participants received an examination with image acquisition. Initially, body parameters and claustrophobia were assessed. The subjects were then rotated to different angles for simulation (0°, 45°, 90°, 180°) and imaging (0°, 70°, 90°, 110°). At each angle, anxiety and motion sickness were assessed using a 6-item State-Trait-Anxiety-Inventory (STAI-6) and a modified Motion Sickness Assessment Questionnaire (MSAQ). In addition, general areas of discomfort were evaluated.
RESULTS
Out of 50 subjects, three (6%) subjects terminated the study prematurely. One subject dropped out during simulation due to nausea while rotating to 45°. During imaging, further two subjects dropped out due to shoulder pain from positioning at 90° and 110°, respectively. The average result for claustrophobia (0 = no claustrophobia to 4 = extreme claustrophobia) was none to light claustrophobia (average score: simulation 0.64 ± 0.33, imaging 0.51 ± 0.39). The mean anxiety scores (0% = no anxiety to 100% = maximal anxiety) were 11.04% (simulation) and 15.82% (imaging). Mean motion sickness scores (0% = no motion sickness to 100% = maximal motion sickness) of 3.5% (simulation) and 6.76% (imaging) were obtained across all participants.
CONCLUSION
Our study proves the feasibility of horizontal rotation in a fully-enclosed rotation system within an MR-scanner. Anxiety scores were low and motion sickness was only a minor influence. Both anxiety and motion sickness showed no angular dependency. Further optimizations with regard to immobilization in the rotation device may increase subject comfort.
Topics: Humans; Prospective Studies; Male; Female; Magnetic Resonance Imaging; Adult; Rotation; Radiotherapy, Image-Guided; Middle Aged; Young Adult; Motion Sickness; Patient Compliance; Anxiety; Healthy Volunteers
PubMed: 38849900
DOI: 10.1186/s13014-024-02461-2 -
Scientific Reports Jun 2024Acclimation to crop niches for thousands of years has made indigenous rice cultivars better suited for stress-prone environments. Still, their response to UV-B...
Acclimation to crop niches for thousands of years has made indigenous rice cultivars better suited for stress-prone environments. Still, their response to UV-B resiliency is unknown. 38 rice landraces were grown in cemented pots in a randomised block design with three replicates under open field conditions in Sambalpur University in the wet season of 2022. Half of the plants in each of the cultivars were administered UV-B radiation at the panicle emergence stage in an adjustable UV-B chamber permitting sunlight, and the effects of the stress on various morpho-physiological features, such as spikelet sterility, flag leaf photosynthetic and flavonoid pigment contents, and lipid peroxidation activities, were estimated for calibration of stress resistance. The experiment identified Swarnaprabha and Lalkain as the most sensitive and resilient to stress respectively, and the differential response between them was further revealed in the expression of genes related to UV-B sensitivity. Subject to the stress, Swarnaprabha exhibited symptoms of injuries, like leaf burns, and a higher loss of various photosynthetic parameters, such as pigment contents, SPAD and Fv/Fm, ETR and qP values, while NPQ increased only in Lalkain. Exposure to UV-B increased the total phenolic and flavonoid contents in Lalkain while depressing them in Swarnaprabha. Such an effect amounted to a higher release of fluorescent energy in the latter. The levels of expression of gene families controlling flavonoid activation and UV-B signal transduction, such as OsWRKY, OsUGT, OsRLCK, OsBZIP, OsGLP, and CPD photolyase were similar in both the cultivars in the control condition. However, exposure to UV-B stress overexpressed them in resilient cultivars only. The magnitude of expression of the genes and the impact of the stress on photosynthetic parameters, phenolic compounds and pubescent hair structure at the panicle emergence stage could be valid indicators among indigenous rice for UV-B tolerance.
Topics: Ultraviolet Rays; Oryza; Photosynthesis; Genetic Variation; Gene Expression Regulation, Plant; Plant Leaves; Flavonoids; Stress, Physiological
PubMed: 38849505
DOI: 10.1038/s41598-024-64134-0