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4.
Front Plant Sci ; 15: 1340287, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38362448

RESUMO

Plants possess intricate defense mechanisms to resist cadmium (Cd) stress, including strategies like metal exclusion, chelation, osmoprotection, and the regulation of photosynthesis, with antioxidants playing a pivotal role. The application of nitrogen (N) and phosphorus (P) fertilizers are reported to bolster these defenses against Cd stress. Several studies investigated the effects of N or P on Cd stress in non-woody plants and crops. However, the relationship between N, P application, and Cd stress resistance in valuable timber trees remains largely unexplored. This study delves into the Cd tolerance mechanisms of Phoebe zhennan, a forest tree species, under various treatments: Cd exposure alone, combined Cd stress with either N or P and Cd stress with both N and P application. Our results revealed that the P application enhanced root biomass and facilitated the translocation of essential nutrients like K, Mn, and Zn. Conversely, N application, especially under Cd stress, significantly inhibited plant growth, with marked reductions in leaf and stem biomass. Additionally, while the application of P resulted in reduced antioxidant enzyme levels, the combined application of N and P markedly amplified the activities of peroxidase by 266.36%, superoxide dismutase by 168.44%, and ascorbate peroxidase by 26.58% under Cd stress. This indicates an amplified capacity of the plant to neutralize reactive oxygen species. The combined treatment also led to effective regulation of nutrient and Cd distribution in roots, shoots, and leaves, illustrating a synergistic effect in mitigating toxic impact of N. The study also highlights a significant alteration in photosynthetic activities under different treatments. The N addition generally reduced chlorophyll content by over 50%, while P and NP treatments enhanced transpiration rates by up to 58.02%. Our findings suggest P and NP fertilization can manage Cd toxicity by facilitating antioxidant production, osmoprotectant, and root development, thus enhancing Cd tolerance processes, and providing novel strategies for managing Cd contamination in the environment.

5.
Sci Total Environ ; 921: 171107, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38387560

RESUMO

Soil contamination by Cr(VI) has attracted widespread attention globally in recent years, but it remains a significant challenge in developing an environmentally friendly and eco-sustainable technique for the disposal of Cr(VI)-contaminated soil. Herein, a sustainable cyclic soil washing system for Cr(VI)-polluted soil remediation and the recovery of washing agents using biochar supported nanoscale zero-valent iron (nZVI-BC) was established. Citric acid (CA) was initially screened to desorb Cr(VI) from contaminated soil, mobilizing Cr from the highly bioaccessible fractions. The nZVI-BC exhibited superior properties for Cr(VI) and Cr(total) removal from spent effluent, allowing effective recovery of the washing agents. The elimination mechanism of Cr(total) by nZVI-BC involved the coordinated actions of electrostatic adsorption, reduction, and co-precipitation. The contributions to Cr(VI) reduction by Fe0, surface-bound Fe(II), and soluble Fe(II) were 0.6 %, 39.8 %, and 59.6 %, respectively. Meanwhile, CA favored the activity of surface-bound Fe(II) and Fe0 in nZVI-BC, enhancing the production of soluble Fe(II) to strengthen Cr(VI) removal. Finally, the recovered washing agent was proven to be reused three times. This study showcases that the combined soil washing using biodegradable chelant CA and effluent treatment by nZVI-BC could be a sustainable and promising strategy for Cr(VI)-contaminated soil remediation.


Assuntos
Recuperação e Remediação Ambiental , Poluentes do Solo , Poluentes Químicos da Água , Ferro , Solo , Poluentes do Solo/análise , Carvão Vegetal , Cromo/análise , Adsorção , Compostos Ferrosos , Poluentes Químicos da Água/análise
6.
Comput Methods Biomech Biomed Engin ; 27(3): 285-295, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36847747

RESUMO

In order to analyze and evaluate the stability of lumbar spine and the risk of cage subsidence after different minimally invasive fusion operations, two finite element models Percutaneous endoscopic posterior lumbar interbody fusion (PE-PLIF) and minimally invasive transforaminal lumbar interbody Fusion (MIS-TLIF) were established. The results showed that compared with MIS-TLIF, PE-PLIF had better segmental stability, lower pedicle screw rod system stress, and lower risk of cage subsidence. The results suggest that the cage with appropriate height should be selected to ensure the segmental stability and avoid the risk of the subsidence caused by the cage with large height.


Assuntos
Procedimentos Cirúrgicos Minimamente Invasivos , Fusão Vertebral , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Vértebras Lombares/cirurgia , Fusão Vertebral/métodos , Endoscopia , Região Lombossacral/cirurgia
7.
Plant Cell Environ ; 47(2): 387-407, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38058262

RESUMO

The escalating impact of climate change and ultraviolet (UV) radiation is subjecting plants to unique combinations of UV-B and drought stress. These combined stressors could have additive, synergistic, or antagonistic effects, but the precise nature of these impacts remains uncertain, hampering our ability to predict plant adaptations approach towards stressors. Our analysis of various studies shows that UV-B or drought conditions detrimentally influence plant growth and health metrics by the enhanced generation of reactive oxygen species causing damage to lipids, proteins, carbohydrates and DNA. Further reducing biomass accumulation, plant height, photosynthetic efficiency, leaf area, and water transpiration, while enhancing stress-related symptoms. In response to UV-B radiation and drought stress, plants exhibit a notable up-regulation of specific acclimation-associated metabolites, including proline, flavonoids, anthocyanins, unsaturated fatty acids, and antioxidants. These metabolites play a pivotal role in conferring protection against environmental stresses. Their biosynthesis and functional roles are potentially modulated by signalling molecules such as hydrogen peroxide, abscisic acid, jasmonic acid, salicylic acid, and ethylene, all of which have associated genetic markers that further elucidate their involvement in stress response pathways. In comparison to single stress, the combination of UV-B and drought induces the plant defence responses and growth retardation which are less-than-additive. This sub-additive response, consistent across different study environments, suggests the possibility of a cross-resistance mechanism. Our outlines imply that the adverse effects of increased drought and UV-B could potentially be mitigated by cross-talk between UV-B and drought regimes utilizing a multidimensional approach. This crucial insight could contribute significantly to refining our understanding of stress tolerance in the face of ongoing global climate change.


Assuntos
Antocianinas , Resiliência Psicológica , Secas , Plantas/efeitos da radiação , Estresse Fisiológico/genética
8.
Brachytherapy ; 23(2): 123-135, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38129211

RESUMO

BACKGROUND: Chemoradiation (CRT) may modulate the immune milieu as an in-situ vaccine. Rapid dose delivery of brachytherapy has unclear impact on T-cell repertoires. HPV-associated cancers express viral oncoproteins E6/E7, which enable tracking antigen/tumor-specific immunity during CRT. METHODS: Thirteen cervical cancer patients on a multi-institutional prospective protocol from 1/2020-1/2023 underwent standard-of-care CRT with pulsed-dose-rate brachytherapy boost (2 fractions). Cervix swabs at various timepoints underwent multiplex DNA deep sequencing of the TCR-ß/CDR3 region with immunoSEQ. Separately, HPV-responsive T-cell clones were also expanded ex vivo. Statistical analysis was via Mann-Whitney-U. RESULTS: TCR productive clonality, templates, frequency, or rearrangements increased post-brachytherapy in 8 patients. Seven patients had E6/E7-responsive evolution over CRT with increased productive templates (ranges: 1.2-50.2 fold-increase from baseline), frequency (1.2-1.7), rearrangements (1.2-40.2), and clonality (1.2-15.4). Five patients had HPV-responsive clonal expansion post-brachytherapy, without changes in HPV non-responsive clones. Epitope mapping revealed VDJ rearrangements targeting cervical cancer-associated antigens in 5 patients. The only two patients with disease recurrence lacked response in all metrics. A lack of global TCR remodeling correlated with worse recurrence-free survival, p = 0.04. CONCLUSION: CRT and brachytherapy alters the cervical cancer microenvironment to facilitate the expansion of specific T-cell populations, which may contribute to treatment efficacy.


Assuntos
Braquiterapia , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/radioterapia , Colo do Útero , Infecções por Papillomavirus/complicações , Linfócitos T , Braquiterapia/métodos , Estudos Prospectivos , Recidiva Local de Neoplasia , Receptores de Antígenos de Linfócitos T , Microambiente Tumoral
9.
Cancer Cell ; 41(11): 1945-1962.e11, 2023 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-37863066

RESUMO

Tumor microbiota can produce active metabolites that affect cancer and immune cell signaling, metabolism, and proliferation. Here, we explore tumor and gut microbiome features that affect chemoradiation response in patients with cervical cancer using a combined approach of deep microbiome sequencing, targeted bacterial culture, and in vitro assays. We identify that an obligate L-lactate-producing lactic acid bacterium found in tumors, Lactobacillus iners, is associated with decreased survival in patients, induces chemotherapy and radiation resistance in cervical cancer cells, and leads to metabolic rewiring, or alterations in multiple metabolic pathways, in tumors. Genomically similar L-lactate-producing lactic acid bacteria commensal to other body sites are also significantly associated with survival in colorectal, lung, head and neck, and skin cancers. Our findings demonstrate that lactic acid bacteria in the tumor microenvironment can alter tumor metabolism and lactate signaling pathways, causing therapeutic resistance. Lactic acid bacteria could be promising therapeutic targets across cancer types.


Assuntos
Microbiota , Neoplasias do Colo do Útero , Feminino , Humanos , Ácido Láctico/metabolismo , Neoplasias do Colo do Útero/radioterapia , Lactobacillus/genética , Lactobacillus/metabolismo , Microambiente Tumoral
10.
Environ Sci Technol ; 57(40): 15087-15098, 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37754765

RESUMO

Bacteria are often exposed to long-term starvation during transportation and storage, during which a series of enzymes and metabolic pathways are activated to ensure survival. However, why the surface color of the bacteria changes during starvation is still not well-known. In this study, we found black anammox consortia suffering from long-term starvation contained 0.86 mmol gVSS-1 cytochrome c, which had no significant discrepancy compared with the red anammox consortia (P > 0.05), indicating cytochrome c was not the key issue for chromaticity change. Conversely, we found that under starvation conditions cysteine degradation is an important metabolic pathway for the blackening of the anammox consortia for H2S production. In particular, anammox bacteria contain large amounts of iron-rich nanoparticles, cytochrome c, and other iron-sulfur clusters that are converted to produce free iron. H2S combines with free iron in bacteria to form Fe-S compounds, which eventually exist stably as FeS2, mainly in the extracellular space. Interestingly, FeS2 could be oxidized by air aeration, which makes the consortia turn red again. The unique self-protection mechanism makes the whole consortia appear black, avoiding inhibition by high concentrations of H2S and achieving Fe storage. This study expands the understanding of the metabolites of anammox bacteria as well as the bacterial survival mechanism during starvation.

11.
J Int Med Res ; 51(8): 3000605231190763, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37561537

RESUMO

Transurethral resection of the prostate (TURP) is the gold-standard classical method for the treatment of benign prostatic hyperplasia (BPH). In minimally invasive surgery, holmium laser enucleation of the prostate (HoLEP) is considered an alternative option. In this systematic review and meta-analysis, we aimed to comprehensively evaluate the advantages and disadvantages of TURP and HoLEP the treating BPH. We comprehensively searched PubMed, Cochrane Library, EMBASE, and Web of Science databases for all randomized controlled trials published before 1 December 2022 comparing HoLEP and TURP. The study protocol is registered on INPLASY (DOI: 10.37766/inplasy2023.5.0065). Compared with TURP, HoLEP required longer operation time but shorter catheter duration, hospital stay, and bladder irrigation time, as well as less postoperative irrigation. With HoLEP, maximum urinary flow rate at 12 and 24 months after surgery; post-void residual volume at 1, 6, and 12 months; and International Prostate Symptom Score at 12 months after surgery were superior to those with TURP. HoLEP was associated with significantly lower risk of hyponatremia, blood transfusion, and urethral stricture but greater risk of postoperative dysuria. Compared with TURP, HoLEP had better curative efficacy at 6, 12, and 24 months after operation and lower incidence of adverse events in patients with BPH.


Assuntos
Terapia a Laser , Lasers de Estado Sólido , Hiperplasia Prostática , Ressecção Transuretral da Próstata , Masculino , Humanos , Próstata , Ressecção Transuretral da Próstata/efeitos adversos , Ressecção Transuretral da Próstata/métodos , Hiperplasia Prostática/cirurgia , Hiperplasia Prostática/etiologia , Lasers de Estado Sólido/uso terapêutico , Terapia a Laser/efeitos adversos , Terapia a Laser/métodos , Hólmio , Resultado do Tratamento
12.
Artigo em Inglês | MEDLINE | ID: mdl-37652157

RESUMO

Problems, such as broken screws, broken rods, and cage subsidence after clinical spinal fusion surgery affect the success rate of fusion surgery and the fixation effect of fusion segments, and these problems still affect the treatment and postoperative recovery of patients. In this study, we used the biomechanical finite element analysis method to analyze and study the fixation effect of three kinds of spinal internal fixation systems on L4-L5 lumbar spine segments in percutaneous endoscopic posterior lumbar interbody fusion (PE-PLIF). The three different fixation systems compared in this study include bilateral pedicle screw fixation (M1); bilateral pedicle screw with cross-link fixation (M2); bilateral pedicle screws with double bent rods fixation (M3). The internal fixation systems with different structures were analyzed with the help of Hypermesh, and Abaqus. It was found that the internal fixation system with double bent rods reduced screw stresses by 23.8 and 22.2% in right and left axial rotation than the traditional bilateral pedicle screw system, while titanium rod stresses were reduced by 9.6, 3.7, 9.6, and 2.9% in flexion, left and right lateral bending, and right axial rotation, respectively, and L5 upper endplate stresses were reduced by 35.5, 18.9, 38.4, 10.2, and 48.3% in flexion, left and right lateral bending, and left and right axial rotation, respectively. The spinal range of motion (ROM) of the M3 internal fixation system was less than that of the M1 and M2 internal fixation systems in left lateral bending, left lateral rotation, and right axial rotation, and the intact vertebral ROM was reduced by 93.7, 94.9, and 90.9%, respectively. The double bent rod structure of the spinal internal fixation system has better biomechanical properties, which can effectively reduce the risk of screw breakage, loosening, cage subsidence, and endplate collapse after fusion surgery.

13.
Micromachines (Basel) ; 14(6)2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37374690

RESUMO

The main motivation of this work was to demonstrate a hollow telescopic rod structure that could be used for minimally invasive surgery. The telescopic rods were fabricated using 3D printing technology to make mold flips. During fabrication, differences in biocompatibility, light transmission, and ultimate displacement were compared between telescopic rods fabricated via different processes, so as to select the appropriate process. To achieve these goals, flexible telescopic rod structures were designed and 3D-printed molds were fabricated using Fused Deposition Modeling (FDM) and Stereolithography (SLA) techniques. The results showed that the three molding processes had no impact on the doping of the PDMS specimens. However, the FDM molding process had lower surface flatness accuracy compared to SLA. The SLA mold flip fabrication exhibited superior surface accuracy and light transmission compared to the other methods. The sacrificial template method and the use of HTL direct demolding technique had no significant impact on cellular activity and biocompatibility, but the mechanical properties of the PDMS specimens were weakened after swelling recovery. The height and radius of the hollow rod were found to have a significant impact on the mechanical properties of the flexible hollow rod. The hyperelastic model was fitted appropriately with the mechanical test results, and the ultimate elongation increased with an increase in hollow-solid ratios under the uniform force.

14.
BMC Surg ; 23(1): 169, 2023 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-37353772

RESUMO

BACKGROUND: Colorectal liver metastases attached major intrahepatic vessels has been considered to be a risk factor for survival outcome after liver resection. The present study aimed to clarify the outcomes of R1 surgery (margin < 1 mm) in CRLM patients, distinguishing parenchymal margin R1 and attached to major intrahepatic vessels R1. METHODS: In present study, 283 CRLM patients who were evaluated to be attached to major intrahepatic vessels initially and underwent liver resection following preoperative chemotherapy. They were assigned to two following groups: R0 (n = 167), R1 parenchymal (n = 58) and R1 vascular (n = 58). The survival outcomes and local recurrence rates were analyzed in each group. RESULTS: Overall, 3- and 5-year overall survival rates after liver resection were 53.0% and 38.2% (median overall survival 37 months). Five-year overall survival was higher in patients with R0 than parenchymal R1 (44.9%% vs. 26.3%, p = 0.009), whereas there was no significant difference from patients with vascular R1 (34.3%, p = 0.752). In the multivariable analysis, preoperative chemotherapy > 4 cycles, clinical risk score 3-5, RAS mutation, parenchymal R1 and CA199 > 100 IU/ml were identified as independent predictive factors of overall survival (p < 0.05). There was no significant difference for local recurrence among three groups. CONCLUSION: Parenchymal R1 resection was independent risk factor for CRLM. Vascular R1 surgery achieved survival outcomes equivalent to R0 resection. Non-anatomic liver resection for CRLM attached to intrahepatic vessels might be pursued to increase patient resectability by preoperative chemotherapy.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Neoplasias Colorretais/cirurgia , Recidiva Local de Neoplasia/cirurgia , Neoplasias Hepáticas/secundário , Hepatectomia , Procedimentos Cirúrgicos Vasculares , Taxa de Sobrevida , Estudos Retrospectivos , Prognóstico
15.
J Hazard Mater ; 456: 131664, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37224716

RESUMO

Terbuthylazine (TBA) is an emerging environmental contaminant that poses moderate to high risk to non-target organisms. In this study, a newly TBA-degrading strain, Agrobacterium rhizogenes AT13, was isolated. This bacterium degraded 98.7% of TBA (100 mg/L) within 39 h. Based on the six detected metabolites, three novel pathways of strain AT13, including dealkylation, deamination-hydroxylation, and ring-opening reactions, were proposed. The risk assessment demonstrated that most degradation products might be substantially less harmful than TBA. Whole-genome sequencing and RT-qPCR analysis revealed that ttzA, which encodes S-adenosylhomocysteine deaminase (TtzA), is closely related to TBA degradation in AT13. Recombinant TtzA showed 75.3% degradation of 50 mg/L of TBA within 13 h and presented a Km value of 0.299 mmol/L and a Vmax value of 0.041 mmol/L/min. The molecular docking results indicated that the binding energy of TtzA to TBA was -32.9 kcal/mol and TtzA residue ASP161 formed two hydrogen bonds with TBA at distances of 2.23 and 1.80 Å. Moreover, AT13 efficiently degraded TBA in water and soil. Overall, this study provides a foundation for the characterization and mechanism of TBA biodegradation and may enhance our understanding of the TBA biodegradation by microbes.


Assuntos
Agrobacterium , Bactérias , Simulação de Acoplamento Molecular , Agrobacterium/genética , Biodegradação Ambiental
16.
Environ Toxicol Chem ; 42(7): 1485-1500, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37097018

RESUMO

Roadside soils are regarded as a reservoir for heavy metal pollution, which potentially leads to ecosystem deterioration as well as serious hazard to human health. A comprehensive investigation was conducted for the levels, relationship with soil properties, and potential sources of heavy metals (Hg, Cu, Zn, Pb, Cd, and Cr) in roadside soils in six cities (Changzhi, Jincheng, Yuncheng, Linfen, Xinzhou, Datong) of Shanxi Province; and the corresponding ecological risk and human health risk associated with the concentrations of heavy metals were addressed. Heavy metal concentrations of 112 roadside soil samples in the surveyed cities were, in decreasing order, Zn, Cu, Cr, Pb, Cd, and Hg, which were higher than corresponding background values. The highest concentrations were in Changzhi. The results of Pearson correlation analysis demonstrated that positive correlations in varying degrees existed between soil properties such as electrical conductivity, total nitrogen, total phosphorus, and total organic carbon with specific heavy metals and that negative correlations were observed for clay and electrical conductivity. Anthropogenic sources related to traffic emissions and industrialization were the main sources of heavy metals in roadside soils according to principal component analysis. The ecological risk assessments were achieved by pollution index and potential risk index, indicating that contamination with Hg was the most serious, which posed the highest risk to the ecosystems in the surveyed cities; and the ecological risk in Changzhi ranked at the top compared with other cities. For the human health risk assessment, the results demonstrated that the noncarcinogenic and carcinogenic risks were in the acceptable range in the surveyed cities. However, there was a higher health risk from heavy metal exposure for children than adults, and the main exposure pathway was soil ingestion. In addition, Changzhi was the city with the highest noncarcinogenic and carcinogenic risks, and the main human health risks were posed by Cr contamination in roadside soil, which was different from the results of ecological risks. Both results of ecological and health risk assessment demonstrated that the higher risk exhibited in southern and southeastern cities than northern cities in Shanxi Province. Environ Toxicol Chem 2023;42:1485-1500. © 2023 SETAC.


Assuntos
Mercúrio , Metais Pesados , Poluentes do Solo , Adulto , Criança , Humanos , Monitoramento Ambiental/métodos , Ecossistema , Solo , Cidades , Cádmio/análise , Chumbo/análise , Poluentes do Solo/análise , Metais Pesados/análise , Mercúrio/análise , China , Medição de Risco
17.
Nat Commun ; 14(1): 1333, 2023 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-36906610

RESUMO

The prototypic cancer-predisposition disease Fanconi Anemia (FA) is identified by biallelic mutations in any one of twenty-three FANC genes. Puzzlingly, inactivation of one Fanc gene alone in mice fails to faithfully model the pleiotropic human disease without additional external stress. Here we find that FA patients frequently display FANC co-mutations. Combining exemplary homozygous hypomorphic Brca2/Fancd1 and Rad51c/Fanco mutations in mice phenocopies human FA with bone marrow failure, rapid death by cancer, cellular cancer-drug hypersensitivity and severe replication instability. These grave phenotypes contrast the unremarkable phenotypes seen in mice with single gene-function inactivation, revealing an unexpected synergism between Fanc mutations. Beyond FA, breast cancer-genome analysis confirms that polygenic FANC tumor-mutations correlate with lower survival, expanding our understanding of FANC genes beyond an epistatic FA-pathway. Collectively, the data establish a polygenic replication stress concept as a testable principle, whereby co-occurrence of a distinct second gene mutation amplifies and drives endogenous replication stress, genome instability and disease.


Assuntos
Neoplasias da Mama , Anemia de Fanconi , Animais , Feminino , Humanos , Camundongos , Proteína BRCA2/genética , Neoplasias da Mama/genética , Proteínas de Ligação a DNA/genética , Anemia de Fanconi/genética , Genótipo , Mutação , Fenótipo
18.
Int J Radiat Oncol Biol Phys ; 116(5): 1043-1054, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-36801350

RESUMO

PURPOSE: Human papillomavirus (HPV) is the primary driver of cervical cancer. Although studies in other malignancies correlated peripheral blood DNA clearance with favorable outcomes, research on the prognostic value of HPV clearance in gynecologic cancers using intratumoral HPV is scarce. We aimed to quantify the intratumoral HPV virome in patients undergoing chemoradiation therapy (CRT) and associate this with clinical characteristics and outcomes. METHODS AND MATERIALS: This prospective study enrolled 79 patients with stage IB-IVB cervical cancer undergoing definitive CRT. Cervical tumor swabs collected at baseline and week 5 (end of intensity modulated radiation therapy) were sent for shotgun metagenome sequencing and processed via VirMAP, a viral genome sequencing and identification tool for all known HPV types. The data were categorized into HPV groups (16, 18, high risk [HR], and low risk [LR]). We used independent t tests and Wilcoxon signed-rank to compare continuous variables and χ2 and Fisher exact tests to compare categorical variables. Kaplan-Meier survival modeling was performed with log-rank testing. HPV genotyping was verified using quantitative polymerase chain reaction to validate VirMAP results using receiver operating characteristic curve and Cohen's kappa. RESULTS: At baseline, 42%, 12%, 25%, and 16% of patients were positive for HPV 16, HPV 18, HPV HR, and HPV LR, respectively, and 8% were HPV negative. HPV type was associated with insurance status and CRT response. Patients with HPV 16+ and other HPV HR+ tumors were significantly more likely to have a complete response to CRT versus patients with HPV 18 and HPV LR/HPV-negative tumors. Overall HPV viral loads predominantly decreased throughout CRT, except for HPV LR viral load. CONCLUSIONS: Rarer, less well-studied HPV types in cervical tumors are clinically significant. HPV 18 and HPV LR/negative tumors are associated with poor CRT response. This feasibility study provides a framework for a larger study of intratumoral HPV profiling to predict outcomes in patients with cervical cancer.


Assuntos
Infecções por Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/patologia , Papillomavirus Humano , Infecções por Papillomavirus/complicações , Estudos Prospectivos , Genótipo , Viroma , Papillomaviridae/genética , DNA Viral/análise
19.
Clin Cancer Res ; 29(1): 154-164, 2023 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-36166093

RESUMO

PURPOSE: Overweight/obese (OW/OB) patients with metastatic melanoma unexpectedly have improved outcomes with immune checkpoint inhibitors (ICI) and BRAF-targeted therapies. The mechanism(s) underlying this association remain unclear, thus we assessed the integrated molecular, metabolic, and immune profile of tumors, as well as gut microbiome features, for associations with patient body mass index (BMI). EXPERIMENTAL DESIGN: Associations between BMI [normal (NL < 25) or OW/OB (BMI ≥ 25)] and tumor or microbiome characteristics were examined in specimens from 782 patients with metastatic melanoma across 7 cohorts. DNA associations were evaluated in The Cancer Genome Atlas cohort. RNA sequencing from 4 cohorts (n = 357) was batch corrected and gene set enrichment analysis (GSEA) by BMI category was performed. Metabolic profiling was conducted in a subset of patients (x = 36) by LC/MS, and in flow-sorted melanoma tumor cells (x = 37) and patient-derived melanoma cell lines (x = 17) using the Seahorse XF assay. Gut microbiome features were examined in an independent cohort (n = 371). RESULTS: DNA mutations and copy number variations were not associated with BMI. GSEA demonstrated that tumors from OW/OB patients were metabolically quiescent, with downregulation of oxidative phosphorylation and multiple other metabolic pathways. Direct metabolite analysis and functional metabolic profiling confirmed decreased central carbon metabolism in OW/OB metastatic melanoma tumors and patient-derived cell lines. The overall structure, diversity, and taxonomy of the fecal microbiome did not differ by BMI. CONCLUSIONS: These findings suggest that the host metabolic phenotype influences melanoma metabolism and provide insight into the improved outcomes observed in OW/OB patients with metastatic melanoma treated with ICIs and targeted therapies. See related commentary by Smalley, p. 5.


Assuntos
Melanoma , Segunda Neoplasia Primária , Humanos , Fatores de Risco , Variações do Número de Cópias de DNA , Obesidade/complicações , Sobrepeso , Melanoma/genética , Melanoma/complicações , Índice de Massa Corporal
20.
Front Bioeng Biotechnol ; 11: 1323266, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38288243

RESUMO

The prevention, control and treatment of cerebral aneurysm (CA) has become a common concern of human society, and by simulating the biomechanical environment of CA using finite element analysis (FEA), the risk of aneurysm rupture can be predicted and evaluated. The target models of the current study are mainly idealized single-layer linear elastic cerebral aneurysm models, which do not take into account the effects of the vessel wall structure, material constitution, and structure of the real CA model on the mechanical parameters. This study proposes a reconstruction method for patient-specific trilaminar CA structural modeling. Using two-way fluid-structure interaction (FSI), we comparatively analyzed the effects of the differences between linear and hyperelastic materials and three-layer and single-layer membrane structures on various hemodynamic parameters of the CA model. It was found that the numerical effects of the different CA membrane structures and material constitution on the stresses and wall deformations were obvious, but does not affect the change in its distribution pattern and had little effect on the blood flow patterns. For the same material constitution, the stress of the three-layer membrane structure were more than 10.1% larger than that of the single-layer membrane structure. For the same membrane structure, the stress of the hyperelastic material were more than 5.4% larger than that of the linear elastic material, and the displacement of the hyperelastic material is smaller than that of the linear elastic material by about 20%. And the maximum value of stress occurred in the media, and the maximum displacement occurred in the intima. In addition, the upper region of the tumor is the maximum rupture risk region for CA, and the neck of the tumor and the bifurcation of the artery are also the sub-rupture risk regions to focus on. This study can provide data support for the selection of model materials for CA simulation and analysis, as well as a theoretical basis for clinical studies and subsequent research methods.

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