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International Journal of Radiation... Jun 2024Adjuvant radiotherapy after radical cystectomy in locally advanced bladder cancer was revived after the advancement in precise radiotherapy that decreased the normal...
BACKGROUND
Adjuvant radiotherapy after radical cystectomy in locally advanced bladder cancer was revived after the advancement in precise radiotherapy that decreased the normal pelvic tissue radiation hazards. However, there are still scarce controlled randomized studies addressing this issue.
PATIENTS AND METHODS
One hundred thirty-one cystectomized urothelial bladder cancer patients were enrolled; a hundred and twenty-two were randomized to receive adjuvant radiotherapy (ART) 50 Gy/25 fractions, 4 weeks' post-cystectomy or cystectomy alone (CY). Sixty-two were included in the ART arm and sixty in the CY arm. Twenty-four ART and 30 CY patients received Neoadjuvant chemotherapy. Eleven patients (9%) had cotenant neo-bladder diversion, 6 in ART, and 5 in CY arms. All ART patients were treated with intensity-modulated radiotherapy (IMRT) with daily verification cone-beam CT (CBCT). The median follow-up was 42.7 months.
RESULTS
The 3-year adjusted Locoregional relapse-free survival (LRFS) rate was higher in the ART arm, measuring 81% (95%CI: 69-94) compared to 71% (95% CI: 60-80) (p=0.0457). ART significantly improved the locoregional relapse-free rate in the cystectomy bed and the pelvic side wall (p= 0.016 and 0.001, respectively). The overall survival, event-free, and distant metastasis-free survival did not rank to the level of statistical significance in the 2 arms. Even though the acute side effects were slightly higher in ART, the late toxicities were almost equal in the two groups.
CONCLUSIONS
Adjuvant radiotherapy is safe and quite tolerable after radical cystectomy when using precise radiation techniques. These techniques significantly improved the LRFS but had insignificant improvement on the overall survival. ART did not affect the distant metastasis-free survival. Similar studies are performed in different centers around the world to confirm the value of ART in urothelial bladder cancer.
PubMed: 38879088
DOI: 10.1016/j.ijrobp.2024.05.012 -
International Immunopharmacology Jun 2024This study aimed to investigate the role of JMJD2A in radiotherapy tolerance of esophageal squamous cell carcinoma (ESCC).
OBJECTIVE
This study aimed to investigate the role of JMJD2A in radiotherapy tolerance of esophageal squamous cell carcinoma (ESCC).
METHODS
The levels of H3K9me3 modification were analyzed in anti-PD-1 therapy non-responder or responder patients, and the expression differences of H3K9me3-related modifying enzymes were assessed in TCGA-ESCC and ICGC cohorts. Subsequently, JMJD2A was knocked down in ESCC cells using CRISPR-Cas9 or lentivirus-mediated shRNA, and changes in malignant behavior of ESCC cells were observed. RNA-seq, ATAC-seq, and ChIP-seq analyses were then conducted to investigate the genes and downstream signaling pathways regulated by JMJD2A, and functional validation experiments were performed to analyze the role of downstream regulated genes and pathways in ESCC malignant behavior and immune evasion.
RESULTS
JMJD2A was significantly overexpressed in ESCC and anti-PD-1 therapy non-responders. Knockdown or deletion of JMJD2A significantly promoted the malignant behavior and immune evasion of ESCC. JMJD2A facilitated the structural changes in chromatin and promoted the binding of SMARCA4 to super-enhancers, thereby inducing the expression of GPX4. This resulted in the inhibition of radiation-induced DNA damage and cell ferroptosis, ultimately promoting the malignant behavior and immune evasion of ESCC cells.
CONCLUSION
JMJD2A plays an indispensable role in the malignant behavior and immune evasion of ESCC. It regulates the binding of SMARCA4 to super-enhancers and affects the chromatin's epigenetic landscape, thereby promoting the expression of GPX4 and attenuating iron-mediated cell death caused by radiotherapy. Consequently, it triggers the malignant behavior and immune evasion of ESCC cells.
PubMed: 38878485
DOI: 10.1016/j.intimp.2024.112401 -
Harmful Algae Jun 2024This study aimed to explore the effects of different light intensities on the ecophysiology of eight new Dinophysis isolates comprising four species (D. acuminata, D....
This study aimed to explore the effects of different light intensities on the ecophysiology of eight new Dinophysis isolates comprising four species (D. acuminata, D. ovum, D. fortii, and D. caudata) collected from different geographical regions in the US. After six months of acclimation, the growth rates, photosynthetic efficiency (F/F ratio), toxin content, and net toxin production rates of the Dinophysis strains were examined. The growth rates of D. acuminata and D. ovum isolates were comparable across light intensities, with the exception of one D. acuminata strain (DANY1) that was unable to grow at the lowest light intensity. However, D. fortii and D. caudata strains were photoinhibited and grew at a slower rate at the highest light intensity, indicating a lower degree of adaptability and tolerance to such conditions. Photosynthetic efficiency was similar for all Dinophysis isolates and negatively correlated with exposure to high light intensities. Multiple toxin metrics, including cellular toxin content and net production rates of DSTs and PTXs, were variable among species and even among isolates of the same species in response to light intensity. A pattern was detected, however, whereby the net production rates of PTXs were significantly lower across all Dinophysis isolates when exposed to the lowest light intensity. These findings provide a basis for understanding the effects of light intensity on the eco-physiological characteristics of Dinophysis species in the US and could be employed to develop integrated physical-biological models for species and strains of interest to predict their population dynamics and mitigate their negative effects.
Topics: Photosynthesis; Light; Dinoflagellida; Acclimatization; Marine Toxins; Species Specificity
PubMed: 38876524
DOI: 10.1016/j.hal.2024.102624 -
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 -
Environmental Monitoring and Assessment Jun 2024The Citarum watershed and the Saguling reservoir are vital natural resources in Indonesia, affecting the livelihood of West Java and the DKI Jakarta population. This...
The Citarum watershed and the Saguling reservoir are vital natural resources in Indonesia, affecting the livelihood of West Java and the DKI Jakarta population. This study aimed to assess the soil erosion in the Upper Citarum watershed and identify its source. The study used the fallout radionuclide technique, geochemical tracers, and an unmixing model to measure soil erosion and the contribution of suspended sediment sources due to erosion. Soil bulk transects and surface soil were sampled using a coring tool on the Ciwidey and Cisangkuy sub-watersheds. Riverbank and suspended sediment samples were collected from tributaries and rivers. With Cs, 40% of the samples had values below the minimum detectable activity, and vice versa for Pb, all samples are detectable. For mitigation, bare land needs to be recovered due to its erosion (25.6 t ha year) exceeding the tolerance erosion value (17 t ha year). Statistically, Mg and Na were the most appropriate composite tracers for suspended sediment contribution. The unmixing model predicted the sediment contributors from bare land (58%), the riverbank (32.7%), and plantation land (9.3%). Proper land conservation could reduce sediment supply by almost 14.7% and extend the reservoir's life. This is the first study to report the feasibility of the unmixing model in Indonesia.
Topics: Indonesia; Environmental Monitoring; Rivers; Soil Erosion; Geologic Sediments; Soil; Cesium Radioisotopes; Conservation of Natural Resources
PubMed: 38871834
DOI: 10.1007/s10661-024-12750-8 -
Nano Letters Jun 2024Radiation-tolerance and repairable flexible transistors and integrated circuits (ICs) with low power consumption have become hot topics due to their wide applications in...
Radiation-tolerance and repairable flexible transistors and integrated circuits (ICs) with low power consumption have become hot topics due to their wide applications in outer space, nuclear power plants, and X-ray imaging. Here, we designed and developed novel flexible semiconducting single-walled carbon nanotube (sc-SWCNT) thin-film transistors (TFTs) and ICs. Sc-SWCNT solid-electrolyte-gate dielectric (SEGD) TFTs showcase symmetric ambipolar characteristics with flat-band voltages (V) of ∼0 V, high I/I ratios (>10), and the recorded irradiation resistance (up to 22 Mrad). Moreover, flexible sc-SWCNT ICs, including CMOS-like inverters and NAND and NOR logic gates, have excellent operating characteristics with low power consumption (≤8.4 pW) and excellent irradiation resistance. Significantly, sc-SWCNT SEGD TFTs and ICs after radiation with a total irradiation dose (TID) ≥ 11 Mrad can be repaired after thermal heating at 100 °C. These outstanding characteristics are attributed to the designed device structures and key core materials including SEGD and sc-SWCNT.
PubMed: 38869197
DOI: 10.1021/acs.nanolett.4c01691 -
Strahlentherapie Und Onkologie : Organ... Jun 2024Pulmonary artery intimal sarcoma (PAIS) is a rare and aggressive malignancy originating from the intimal layer of the pulmonary artery with poor prognosis due to its...
Pulmonary artery intimal sarcoma (PAIS) is a rare and aggressive malignancy originating from the intimal layer of the pulmonary artery with poor prognosis due to its aggressive nature. The management of PAIS poses both diagnostic and therapeutic challenges. It presents with nonspecific symptoms and is often misdiagnosed as pulmonary embolism. While surgical resection is the primary treatment modality, the role of adjuvant chemotherapy and radiotherapy remains uncertain. However, given the high recurrence rate, adjuvant chemotherapy and/or radiotherapy have been utilized in a limited number of case reports. We present the case of a 46-year-old woman who was diagnosed with PAIS and underwent surgical resection followed by adjuvant chemotherapy (ChT) and radiotherapy (RT), demonstrating good tolerance to this multimodal treatment approach.
PubMed: 38866999
DOI: 10.1007/s00066-024-02250-6 -
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 -
Advances in Immunology 2024The intestine represents the most complex cellular network in the whole body. It is constantly faced with multiple types of immunostimulatory agents encompassing from... (Review)
Review
The intestine represents the most complex cellular network in the whole body. It is constantly faced with multiple types of immunostimulatory agents encompassing from food antigen, gut microbiome, metabolic waste products, and dead cell debris. Within the intestine, most T cells are found in three primary compartments: the organized gut-associated lymphoid tissue, the lamina propria, and the epithelium. The well-orchestrated epithelial-immune-microbial interaction is critically important for the precise immune response. The main role of intestinal mesenchymal stromal cells is to support a structural framework within the gut wall. However, recent evidence from stromal cell studies indicates that they also possess significant immunomodulatory functions, such as maintaining intestinal tolerance via the expression of PDL1/2 and MHC-II molecules, and promoting the development of CD103 dendritic cells, and IgA plasma cells, thereby enhancing intestinal homeostasis. In this review, we will summarize the current understanding of CD8 T cells and stromal cells alongside the intestinal tract and discuss the reciprocal interactions between T subsets and mesenchymal stromal cell populations. We will focus on how the tissue residency, migration, and function of CD8 T cells could be potentially regulated by mesenchymal stromal cell populations and explore the molecular mediators, such as TGF-β, IL-33, and MHC-II molecules that might influence these processes. Finally, we discuss the potential pathophysiological impact of such interaction in intestine hemostasis as well as diseases of inflammation, infection, and malignancies.
Topics: Humans; Mesenchymal Stem Cells; Animals; CD8-Positive T-Lymphocytes; Homeostasis; Intestinal Mucosa; Cell Communication; Intestines
PubMed: 38866438
DOI: 10.1016/bs.ai.2024.02.001 -
Applied and Environmental Microbiology Jun 2024The extremophile maintains a highly organized and condensed nucleoid as its default state, possibly contributing to its high tolerance to ionizing radiation (IR)....
The extremophile maintains a highly organized and condensed nucleoid as its default state, possibly contributing to its high tolerance to ionizing radiation (IR). Previous studies of the nucleoid were limited by reliance on manual image annotation and qualitative metrics. Here, we introduce a high-throughput approach to quantify the geometric properties of cells and nucleoids using confocal microscopy, digital reconstructions of cells, and computational modeling. We utilize this novel approach to investigate the dynamic process of nucleoid condensation in response to IR stress. Our quantitative analysis reveals that at the population level, exposure to IR induced nucleoid compaction and decreased the size of cells. Morphological analysis and clustering identified six distinct sub-populations across all tested experimental conditions. Results indicate that exposure to IR induced fractional redistributions of cells across sub-populations to exhibit morphologies associated with greater nucleoid condensation and decreased the abundance of sub-populations associated with cell division. Nucleoid-associated proteins (NAPs) may link nucleoid compaction and stress tolerance, but their roles in regulating compaction in are unknown. Imaging of genomic mutants of known and suspected NAPs that contribute to nucleoid condensation found that deletion of nucleic acid-binding proteins, not previously described as NAPs, can remodel the nucleoid by driving condensation or decondensation in the absence of stress and that IR increased the abundance of these morphological states. Thus, our integrated analysis introduces a new methodology for studying environmental influences on bacterial nucleoids and provides an opportunity to further investigate potential regulators of nucleoid condensation.IMPORTANCE, an extremophile known for its stress tolerance, constitutively maintains a highly condensed nucleoid. Qualitative studies have described nucleoid behavior under a variety of conditions. However, a lack of quantitative data regarding nucleoid organization and dynamics has limited our understanding of the regulatory mechanisms controlling nucleoid organization in . Here, we introduce a quantitative approach that enables high-throughput quantitative measurements of subcellular spatial characteristics in bacterial cells. Applying this to wild-type or single-protein-deficient populations of subjected to ionizing radiation, we identified significant stress-responsive changes in cell shape, nucleoid organization, and morphology. These findings highlight this methodology's adaptability and capacity for quantitatively analyzing the cellular response to stressors for screening cellular proteins involved in bacterial nucleoid organization.
PubMed: 38864629
DOI: 10.1128/aem.00108-24