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1.
Front Oncol ; 14: 1430971, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39091922

RESUMO

Three main areas of research revolve around extracellular vesicles (EVs): their use as early detection diagnostics for cancer prevention, engineering of EVs or other enveloped viral-like particles for therapeutic purposes and to understand how EVs impact biological processes. When investigating the biology of EVs, it is important to consider strategies able to track and alter EVs directly in vivo, as they are released by donor cells. This can be achieved by suitable engineering of EV donor cells, either before implantation or directly in vivo. Here, we make a case for the study of native EVs, that is, EVs released by cells living within a tissue. Novel genetic approaches to detect intercellular communications mediated by native EVs and profile recipient cells are discussed. The use of Rab35 dominant negative mutant is proposed for functional in vivo studies on the roles of native EVs. Ultimately, investigations on native EVs will tremendously advance our understanding of EV biology and open novel opportunities for therapy and prevention.

3.
Cancers (Basel) ; 16(15)2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39123490

RESUMO

INTRODUCTION: Leukemia history affects some radical prostatectomy (RP) patients. Although its prevalence and effect as an adverse risk factor are well known in cardiac surgery, the number of RP patients with a leukemia history, as well as their rate of adverse in-hospital outcomes, are unknown. METHODS: We identified RP patients (National Inpatient Sample 2000-2019), stratified according to the presence or absence of a leukemia history. Descriptive analyses, propensity score matching (PSM, ratio 1:10), and multivariable logistic regression models were used. RESULTS: Of 259,939 RP patients, 416 (0.2%) had a leukemia history. Their proportion increased from 0.1 to 0.2% covering the study span (p < 0.01). Leukemia history patients were older (median age, 64 vs. 62 years, p < 0.001). After PSM for age, insurance status, ethnicity, pelvic lymph node dissection, and Charlson Comorbidity Index, leukemia history RP patients exhibited higher rates of acute kidney injury (<2.6 vs. 0.9%; Odds Ratio [OR] 2.0, p = 0.02), more frequently underwent dialysis (3.6 vs. 1.9%; OR 1.9, p = 0.03), and more frequently had a length of stay exceeding one week (4.8 vs. 2.5%; OR 2.0, p = 0.006). CONCLUSIONS: Although leukemia history RP patients are rare, their numbers have increased. Renal complications and extended hospital stays are more frequent in those individuals.

5.
Polymers (Basel) ; 16(13)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-39000675

RESUMO

In medicine, the occurrence of antibiotic resistance was becoming a critical concern. At the same time, traditional synthesis methods of antibacterial agents often lead to environmental pollution due to the use of toxic chemicals. To address these problems, this study applies the green synthesis method to create a novel composite using a polymer blend (M8) consisting of chitosan (CS), polyethylene glycol (PEG), polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), and silver nanoparticles. The results show that the highest ratio of AgNO3:M8 was 0.15 g/60 mL, which resulted in a 100% conversion of Ag+ to Ag0 after 10 h of reaction at 80 °C. Hence, using M8, Ag nanoparticles (AgNPs) were synthesized at the average size of 42.48 ± 10.77 nm. The AgNPs' composite (M8Ag) was used to inhibit the growth of Staphylococcus aureus (SA), Pseudomonas aeruginosa (PA), and Salmonella enterica (SAL). At 6.25% dilution of M8Ag, the growth of these mentioned bacteria was inhibited. At the same dilution percentage of M8Ag, PA was killed.

6.
ArXiv ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-39040646

RESUMO

Radiation therapy (RT) is one of the most effective treatments for cancer, and its success relies on the accurate delineation of targets. However, target delineation is a comprehensive medical decision that currently relies purely on manual processes by human experts. Manual delineation is time-consuming, laborious, and subject to interobserver variations. Although the advancements in artificial intelligence (AI) techniques have significantly enhanced the auto-contouring of normal tissues, accurate delineation of RT target volumes remains a challenge. In this study, we propose a visual language model-based RT target volume auto-delineation network termed Radformer. The Radformer utilizes a hierarchical vision transformer as the backbone and incorporates large language models to extract text-rich features from clinical data. We introduce a visual language attention module (VLAM) for integrating visual and linguistic features for language-aware visual encoding (LAVE). The Radformer has been evaluated on a dataset comprising 2985 patients with head-and-neck cancer who underwent RT. Metrics, including the Dice similarity coefficient (DSC), intersection over union (IOU), and 95th percentile Hausdorff distance (HD95), were used to evaluate the performance of the model quantitatively. Our results demonstrate that the Radformer has superior segmentation performance compared to other state-of-the-art models, validating its potential for adoption in RT practice.

7.
Artigo em Inglês | MEDLINE | ID: mdl-39009321

RESUMO

Locally recurrent nasopharyngeal carcinoma (NPC) presents substantial challenges in clinical management. Although postoperative re-irradiation (re-RT) has been acknowledged as a potential treatment option, standardized guidelines and consensus regarding the use of re-RT in this context are lacking. This article provides a comprehensive review and summary of international recommendations on postoperative management for potentially resectable locally recurrent NPC, with a special focus on postoperative re-RT. A thorough search was conducted to identify relevant studies on postoperative re-RT for locally recurrent NPC. Controversial issues, including resectability criteria, margin assessment, indications for postoperative re-RT, and the optimal dose and method of re-RT, were addressed through a Delphi consensus process. The consensus recommendations emphasize the need for a clearer and broader definition of resectability, highlighting the importance of achieving clear surgical margins, preferably through an en bloc approach with frozen section margin assessment. Furthermore, these guidelines suggest considering re-RT for patients with positive or close margins. Optimal postoperative re-RT doses typically range around 60 Gy, and hyperfractionation has shown promise in reducing toxicity. These guidelines aim to assist clinicians in making evidence-based decisions and improving patient outcomes in the management of potentially resectable locally recurrent NPC. By addressing key areas of controversy and providing recommendations on resectability, margin assessment, and re-RT parameters, these guidelines serve as a valuable resource for clinical experts involved in the treatment of locally recurrent NPC.

8.
Genes Dev ; 38(11-12): 569-582, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-38997156

RESUMO

Salivary gland homeostasis and regeneration after radiotherapy depend significantly on progenitor cells. However, the lineage of submandibular gland (SMG) progenitor cells remains less defined compared with other normal organs. Here, using a mouse strain expressing regulated CreERT2 recombinase from the endogenous Tert locus, we identify a distinct telomerase-expressing (TertHigh) cell population located in the ductal region of the adult SMG. These TertHigh cells contribute to ductal cell generation during SMG homeostasis and to both ductal and acinar cell renewal 1 year after radiotherapy. TertHigh cells maintain self-renewal capacity during in vitro culture, exhibit resistance to radiation damage, and demonstrate enhanced proliferative activity after radiation exposure. Similarly, primary human SMG cells with high Tert expression display enhanced cell survival after radiotherapy, and CRISPR-activated Tert in human SMG spheres increases proliferation after radiation. RNA sequencing reveals upregulation of "cell cycling" and "oxidative stress response" pathways in TertHigh cells following radiation. Mechanistically, Tert appears to modulate cell survival through ROS levels in SMG spheres following radiation damage. Our findings highlight the significance of TertHigh cells in salivary gland biology, providing insights into their response to radiotherapy and into their use as a potential target for enhancing salivary gland regeneration after radiotherapy.


Assuntos
Homeostase , Regeneração , Telomerase , Telomerase/metabolismo , Telomerase/genética , Animais , Homeostase/genética , Homeostase/efeitos da radiação , Camundongos , Regeneração/efeitos da radiação , Regeneração/genética , Humanos , Glândulas Salivares/efeitos da radiação , Glândulas Salivares/metabolismo , Glândulas Salivares/citologia , Proliferação de Células/efeitos da radiação , Proliferação de Células/genética , Sobrevivência Celular/efeitos da radiação , Sobrevivência Celular/genética , Glândula Submandibular/efeitos da radiação , Glândula Submandibular/metabolismo , Células-Tronco/efeitos da radiação , Células-Tronco/metabolismo , Células-Tronco/citologia , Radioterapia/efeitos adversos , Espécies Reativas de Oxigênio/metabolismo , Células Cultivadas
9.
ArXiv ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-39010876

RESUMO

Radiotherapy treatment planning is a time-consuming and potentially subjective process that requires the iterative adjustment of model parameters to balance multiple conflicting objectives. Recent advancements in large foundation models offer promising avenues for addressing the challenges in planning and clinical decision-making. This study introduces GPT-RadPlan, a fully automated treatment planning framework that harnesses prior radiation oncology knowledge encoded in multi-modal large language models, such as GPT-4Vision (GPT-4V) from OpenAI. GPT-RadPlan is made aware of planning protocols as context and acts as an expert human planner, capable of guiding a treatment planning process. Via in-context learning, we incorporate clinical protocols for various disease sites as prompts to enable GPT-4V to acquire treatment planning domain knowledge. The resulting GPT-RadPlan agent is integrated into our in-house inverse treatment planning system through an API. The efficacy of the automated planning system is showcased using multiple prostate and head & neck cancer cases, where we compared GPT-RadPlan results to clinical plans. In all cases, GPT-RadPlan either outperformed or matched the clinical plans, demonstrating superior target coverage and organ-at-risk sparing. Consistently satisfying the dosimetric objectives in the clinical protocol, GPT-RadPlan represents the first multimodal large language model agent that mimics the behaviors of human planners in radiation oncology clinics, achieving remarkable results in automating the treatment planning process without the need for additional training.

10.
Genomics Inform ; 22(1): 2, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38907330

RESUMO

Small auxin-up RNA (SAUR) proteins were known as a large family that supposedly participated in various biological processes in higher plant species. However, the SAUR family has been still not explored in cacao (Theobroma cacao L.), one of the most important industrial trees. The present work, as an in silico study, revealed comprehensive aspects of the structure, phylogeny, and expression of TcSAUR gene family in cacao. A total of 90 members of the TcSAUR gene family have been identified and annotated in the cacao genome. According to the physic-chemical features analysis, all TcSAUR proteins exhibited slightly similar characteristics. Phylogenetic analysis showed that these TcSAUR proteins could be categorized into seven distinct groups, with 10 sub-groups. Our results suggested that tandemly duplication events, segmental duplication events, and whole genome duplication events might be important in the growth of the TcSAUR gene family in cacao. By re-analyzing the available transcriptome databases, we found that a number of TcSAUR genes were exclusively expressed during the zygotic embryogenesis and somatic embryogenesis. Taken together, our study will be valuable to further functional characterizations of candidate TcSAUR genes for the genetic engineering of cacao.

11.
Cancers (Basel) ; 16(11)2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38893130

RESUMO

The quality of radiation therapy (RT) treatment plans directly affects the outcomes of clinical trials. KBP solutions have been utilized in RT plan quality assurance (QA). In this study, we evaluated the quality of RT plans for brain and head/neck cancers enrolled in multi-institutional clinical trials utilizing a KBP approach. The evaluation was conducted on 203 glioblastoma (GBM) patients enrolled in NRG-BN001 and 70 nasopharyngeal carcinoma (NPC) patients enrolled in NRG-HN001. For each trial, fifty high-quality photon plans were utilized to build a KBP photon model. A KBP proton model was generated using intensity-modulated proton therapy (IMPT) plans generated on 50 patients originally treated with photon RT. These models were then applied to generate KBP plans for the remaining patients, which were compared against the submitted plans for quality evaluation, including in terms of protocol compliance, target coverage, and organ-at-risk (OAR) doses. RT plans generated by the KBP models were demonstrated to have superior quality compared to the submitted plans. KBP IMPT plans can decrease the variation of proton plan quality and could possibly be used as a tool for developing improved plans in the future. Additionally, the KBP tool proved to be an effective instrument for RT plan QA in multi-center clinical trials.

12.
Adv Radiat Oncol ; 9(7): 101504, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38846487

RESUMO

Purpose: Recruiting prospective physicians to radiation oncology can be challenging, because of limited familiarity with the field. The Assistant Clinical Research Coordinator (ACRC) program can help provide trainees early exposure to radiation oncology. Methods and Materials: The ACRC program involves hiring a college graduate to provide administrative and research support for faculty members. The program was developed with our institution's clinical trials office, which provided guidance on regulatory compliance and training. A structured selection process identifies top candidates, and a rigorous onboarding process ensures smooth transitions between ACRCs. We report characteristics and outcomes of ACRC employees and surveyed them to assess their program experience using a Likert scale. Results: From 2005 to 2023, the ACRC program paired 73 ACRCs with faculty. Most faculty (68%) are currently supported by ACRCs. In 2023, 113 applications were received for 4 positions. ACRCs have contributed to research publications (293 as coauthors and 43 as first authors) and taken on leadership roles in the department. Most program alumni have attended medical school (34 of 64 program graduates; 53%). Eight have chosen to specialize in radiation oncology (13%; 2 applying into radiation oncology, 1 in residency, and 5 attendings). Of the 25% of alumni who responded to our survey, 77% responded that the mentorship provided by the ACRC program was very or extremely effective in guiding their academic development. All respondents rated the research opportunities as good or excellent, and 77% rated the clinical experience opportunities as good or excellent. Most (77%) reported that the ACRC program had substantial or significant influence on their choice of career path. Conclusions: The ACRC program provides an opportunity to address recruitment challenges in radiation oncology by offering early exposure to the field, clinical research skills, and mentorship. With the strong interest in our job posting this year, there is potential to expand this program to other institutions.

13.
Nat Commun ; 15(1): 4450, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38789411

RESUMO

Histone deacetylases (HDACs) play a crucial role in transcriptional regulation and are implicated in various diseases, including cancer. They are involved in histone tail deacetylation and canonically linked to transcriptional repression. Previous studies suggested that HDAC recruitment to cell-cycle gene promoters via the retinoblastoma (RB) protein or the DREAM complex through SIN3B is essential for G1/S and G2/M gene repression during cell-cycle arrest and exit. Here we investigate the interplay among DREAM, RB, SIN3 proteins, and HDACs in the context of cell-cycle gene repression. Knockout of SIN3B does not globally derepress cell-cycle genes in non-proliferating HCT116 and C2C12 cells. Loss of SIN3A/B moderately upregulates several cell-cycle genes in HCT116 cells but does so independently of DREAM/RB. HDAC inhibition does not induce general upregulation of RB/DREAM target genes in arrested transformed or non-transformed cells. Our findings suggest that E2F:RB and DREAM complexes can repress cell-cycle genes without relying on HDAC activity.


Assuntos
Fatores de Transcrição E2F , Histona Desacetilases , Proteínas Repressoras , Proteína do Retinoblastoma , Humanos , Histona Desacetilases/metabolismo , Histona Desacetilases/genética , Células HCT116 , Proteínas Repressoras/metabolismo , Proteínas Repressoras/genética , Fatores de Transcrição E2F/metabolismo , Fatores de Transcrição E2F/genética , Proteína do Retinoblastoma/metabolismo , Proteína do Retinoblastoma/genética , Camundongos , Animais , Complexo Correpressor Histona Desacetilase e Sin3/metabolismo , Complexo Correpressor Histona Desacetilase e Sin3/genética , Proteínas Interatuantes com Canais de Kv/metabolismo , Proteínas Interatuantes com Canais de Kv/genética , Ciclo Celular/genética , Regiões Promotoras Genéticas/genética , Regulação da Expressão Gênica , Genes cdc
14.
Exp Eye Res ; 244: 109940, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38782178

RESUMO

Posterior Capsule Opacification (PCO), the most frequent complication of cataract surgery, is caused by the infiltration and proliferation of lens epithelial cells (LECs) at the interface between the intraocular lens (IOL) and posterior lens capsule (PLC). According to the "no space, no cells, no PCO" theory, high affinity (or adhesion force) between the IOL and PLC would decrease the IOL: PLC interface space, hinder LEC migration, and thus reduce PCO formation. To test this hypothesis, an in vitro hemisphere-shaped simulated PLC (sPLC) was made to mimic the human IOL: PLC physical interactions and to assess their influence on LEC responses. Three commercially available IOLs with different affinities/adhesion forces toward the sPLC, including Acrylic foldable IOL, Silicone IOL, and PMMA IOL, were used in this investigation. Using the system, the physical interactions between IOLs and sPLC were quantified by measuring the adhesion force and interface space using an adhesion force apparatus and Optical Coherence Tomography, respectively. Our data shows that high adhesion force and tight binding between IOL and sPLC contribute to a small interface space (or "no space"). By introducing LECs into the in vitro system, we found that, with small interface space, among all IOLs, acrylic foldable IOLs permitted the least extent of LEC infiltration, proliferation, and differentiation (or "no cells"). Further statistical analyses using clinical data revealed that weak LEC responses are associated with low clinical PCO incidence rates (or "no PCO"). The findings support that the in vitro system could simulate IOL: PLC interplays and predict IOLs' PCO potential in support of the "no space, no cells, no PCO" hypothesis.


Assuntos
Opacificação da Cápsula , Células Epiteliais , Lentes Intraoculares , Cápsula Posterior do Cristalino , Células Epiteliais/metabolismo , Humanos , Opacificação da Cápsula/patologia , Cápsula Posterior do Cristalino/patologia , Cápsula Posterior do Cristalino/metabolismo , Proliferação de Células/fisiologia , Movimento Celular/fisiologia , Células Cultivadas
15.
Cancer Epidemiol Biomarkers Prev ; 33(7): 884-895, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38695706

RESUMO

BACKGROUND: Screening with anti-Epstein-Barr virus (EBV) serology and endoscopy decreased nasopharyngeal carcinoma (NPC) mortality in Guangdong in a randomized trial. We conducted a secondary analysis of this trial using local incidence and cost data to optimize screening programs, hypothesizing that screening could be cost-effective in southern China. METHODS: Screening costs and life-years after NPC diagnosis were obtained from the Guangdong trial's intent-to-screen population (men and women aged 30-69). Seropositive subjects were rescreened annually for 5 years. Thereafter, we evaluated 12 screening strategies in Guangdong and Guangxi using a validated model. Strategies used combinations of serology, nasopharyngeal swab PCR (NP PCR), endoscopy, and MRI from trial subcohorts. Incidence data and costs were obtained from local cancer registries and the provincial healthcare system. RESULTS: In the intent-to-screen population, screening with serology and endoscopy was cost-effective (¥42,366/life-year, 0.52 GDP per capita). Screening for 5 to 15 years between ages 35 and 59 years met a willingness-to-pay threshold of 1.5 GDP/quality-adjusted life-years in all modeled populations. Despite doubling costs, adding MRI could be cost-effective via improved sensitivity. NP PCR triage reduced endoscopy/MRI referrals by 37%. One-lifetime screen could reduce NPC mortality by approximately 20%. CONCLUSIONS: EBV-based serologic screening for NPC is likely to be cost-effective in southern China. Among seropositive subjects, the preferred strategies use endoscopy alone or selective endoscopy triaged by MRI with or without NP PCR. These data may aid the design of screening programs in this region. IMPACT: These findings support population-based screening in southern China by defining the target population, cost-effectiveness, and optimized screening approach.


Assuntos
Análise Custo-Benefício , Detecção Precoce de Câncer , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Feminino , Pessoa de Meia-Idade , China/epidemiologia , Masculino , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/virologia , Carcinoma Nasofaríngeo/economia , Adulto , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/economia , Neoplasias Nasofaríngeas/virologia , Detecção Precoce de Câncer/economia , Detecção Precoce de Câncer/métodos , Idoso , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/complicações , Programas de Rastreamento/economia , Programas de Rastreamento/métodos
16.
Food Sci Nutr ; 12(4): 2679-2691, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38628185

RESUMO

Soursop (Annona muricata L.) fruit tea is a health-beneficial product that promotes economic development and addresses the issue of excessive agricultural waste. Prolonging the shelf-life of soursop fruit tea has been of scientific interest currently. This study evaluated the effects of three types of packaging materials of soursop fruit tea (e.g., paper, paper-combined Polyetylen (PE), and aluminum-combined PE) and different storage temperatures (5, 15, 30, and 45°C) on various product characteristics, total polyphenol content (TPC), total flavonoid content (TFC), total ascorbic acid (TAA), and 2,2-diphenyl-1-picryl hydrazyl (DPPH)/2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radical scavenging capacity during 4 weeks of storage. The results revealed that the sample stored in aluminum-combined PE packaging at 30°C retained most of the product's characteristics and nutritional values. This was evidenced by the moisture content of 2.49%, TAA of 3.9 ± 1.4 mg/100 g dry weight, TPC of 12.89 ± 0.47 mgGAE/g, TFC of 0.54 ± 0.004 mgQE/g, DPPH scavenging activity of 4.06 ± 0.02 mgAA/g, and ABTS scavenging activity of 13.34 ± 0.32 mgAA/g. Additionally, the microbiological quality of the sample met the standard of TCVN 9740:2013. Overall, the study highlights the importance of packaging materials and storage temperatures to maintain the nutritional quality of soursop fruit tea. It provides valuable insights into the suitable storage conditions for preserving the quality and health-promoting effects of this product.

17.
Urol Int ; 108(4): 285-291, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38447555

RESUMO

INTRODUCTION: Despite the prospective randomized controlled JAVELIN Bladder 100 trial, no real-world evidence exists regarding tumor characteristics, adverse events (AEs), and survival of avelumab maintenance (AVM)-treated patients with partial/complete response or stable disease after previous platinum-based chemotherapy for advanced/metastatic urothelial carcinoma (mUC). METHODS: We relied on our institutional database to identify mUC patients who received AVM between January, 2021 and December, 2023. The main outcomes consisted of overall survival (OS) and progression-free survival (PFS) and were computed by Kaplan-Meier estimates. Stratification was performed according to programmed death ligand 1 (PD-L1) status. RESULTS: Overall, 24 AVM patients were identified at a median age of 71 (interquartile range [IQR]: 67-76) years, of which 67% were males. Of these, 63%, 21%, and 17% received AVM therapy for bladder cancer and upper tract urothelial carcinoma or both, respectively. PD-L1 status was positive in 45% of patients. During AVM treatment, AEs were observed in 33% of patients; however, they were limited to ≤2 grade AEs. At a median follow-up of eight (IQR 4-20) months, 71% of patients had progressed under AVM with median PFS of 6.2 months (confidence interval [CI]: 3.2-18.2). Median OS was 13.4 (CI: 6.9 - not reached [NR]) months. One-year OS after AVM was 52%. In PD-L1-positive patients, median PFS and OS were 6.4 (CI: 2.7 - NR) months and 13.4 (CI: 7.7 months - NR), respectively. CONCLUSION: AVM is associated with moderate AE rates. Despite similarities in baseline characteristics compared to trial-selected JAVELIN Bladder 100 mUC patients, AVM resulted in longer/similar PFS but significantly shorter OS in real-world setting.


Assuntos
Anticorpos Monoclonais Humanizados , Antineoplásicos Imunológicos , Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Masculino , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Feminino , Idoso , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/secundário , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Taxa de Sobrevida , Quimioterapia de Manutenção , Estudos Retrospectivos , Metástase Neoplásica , Resultado do Tratamento , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/patologia , Pessoa de Meia-Idade
18.
FEBS Lett ; 598(4): 446-456, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38339784

RESUMO

Whereas extracellular vesicles (EVs) have been engineered for cargo loading, innovative strategies for it can still be developed. Here, we describe domain 4 (D4), a cholesterol-binding domain derived from perfringolysin O, as a viable candidate for EV cargo loading. D4 and its mutants localized to the plasma membrane and the membranes of different vesicular structures in the cytoplasm, and facilitate the transport of proteins of interest (POIs) into EVs. D4-EVs were internalized by recipient cells analogous to EVs engineered with CD9. Intracellular cargo discharge from D4-EVs was successfully detected with the assistance of vesicular stomatitis virus glycoprotein. This study presents a novel strategy for recruiting POIs into EVs via a lipid-binding domain that ensures content release in recipient cells.


Assuntos
Toxinas Bacterianas , Vesículas Extracelulares , Proteínas Hemolisinas , Vesículas Extracelulares/metabolismo , Membrana Celular , Toxinas Bacterianas/metabolismo , Lipídeos
19.
Lancet Oncol ; 25(3): 366-375, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38423050

RESUMO

BACKGROUND: The increased incidence of human papillomavirus (HPV)-related cancers has motivated efforts to optimise treatment for these patients with excellent prognosis. Validation of surrogates for overall survival could expedite the investigation of new therapies. We sought to evaluate candidate intermediate clinical endpoints in trials assessing definitive treatment of p16-positive oropharyngeal cancer with chemotherapy or radiotherapy. METHODS: We did a retrospective review of five multicentre, randomised trials (NRG/RTOG 9003, 0129, 0234, 0522, and 1016) that tested radiotherapy with or without chemotherapy in patients (aged ≥18 years) with p16-positive localised head or neck squamous-cell carcinomas. Eight intermediate clinical endpoints were considered as potential surrogates for overall survival: freedom from local progression, freedom from regional progression, freedom from distant metastasis, freedom from locoregional progression, freedom from any progression, locoregional progression-free survival, progression-free survival, and distant metastasis-free survival. We used a two-stage meta-analytical framework, which requires high correlation between the intermediate clinical endpoint and overall survival at the patient level (condition 1), and high correlation between the treatment effect on the intermediate clinical endpoint and the treatment effect on overall survival (condition 2). For both, an r2 greater than 0·7 was used as criteria for clinically relevant surrogacy. FINDINGS: We analysed 1373 patients with oropharyngeal cancer from May 9, 2020, to Nov 22, 2023. 1231 (90%) of patients were men, 142 (10%) were women, and 1207 (88%) were White, with a median age of 57 years (IQR 51-62). Median follow-up was 4·2 years (3·1-5·1). For the first condition, correlating the intermediate clinical endpoints with overall survival at the individual and trial level, the three composite endpoints of locoregional progression-free survival (Kendall's τ 0·91 and r2 0·72), distant metastasis-free survival (Kendall's τ 0·93 and r2 0·83), and progression-free survival (Kendall's τ 0·88 and r2 0·70) were highly correlated with overall survival at the patient level and at the trial-group level. For the second condition, correlating treatment effects of the intermediate clinical endpoints and overall survival, the composite endpoints of locoregional progression-free survival (r2 0·88), distant metastasis-free survival (r2 0·96), and progression-free survival (r2 0·92) remained strong surrogates. Treatment effects on the remaining intermediate clinical endpoints were less strongly correlated with overall survival. INTERPRETATION: We identified locoregional progression-free survival, distant metastasis-free survival, and progression-free survival as surrogates for overall survival in p16-positive oropharyngeal cancers treated with chemotherapy or radiotherapy, which could serve as clinical trial endpoints. FUNDING: NRG Oncology Operations, NRG Oncology SDMC, the National Cancer Institute, Eli Lilly, Aventis, and the University of Michigan.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Orofaríngeas , Masculino , Humanos , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/terapia , Carcinoma de Células Escamosas/terapia , Motivação , Biomarcadores
20.
Environ Sci Pollut Res Int ; 31(11): 16571-16582, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38321276

RESUMO

Parabens (p-hydroxybenzoic acid esters) commonly used preservatives (in cosmetics, pharmaceuticals, and foods) can pose potential effects on environmental health. In this study, seven parabens were quantified in marine fish samples using an ultra-high performance liquid chromatography triple quadrupole mass spectrometer (UHPLC-MS/MS) system. Parabens in the fish samples were extracted and purified by a rapid, simple, and effective procedure comprising sample homogenization with solvent, solid-phase extraction clean-up, and solvent evaporation. Results demonstrated that the recoveries of seven compounds (with relative standard deviation < 15%) were 88-103% in matrix-spike samples and 86-105% in surrogate standards. The method detection limits and method quantification limits of seven parabens were 0.015-0.030 and 0.045-0.090 ng/g-ww (wet weight), respectively. The optimized method was applied to measure the concentration of parabens in the 37 marine fish samples collected from Vietnam coastal waters. The concentration ranges of seven parabens found in round scad and greater lizardfish samples were 6.82-25.3 ng/g ww and 6.21-17.2 ng/g-ww, respectively. Among parabens, methylparaben accounted for the highest contribution in both fish species (43.2 and 44.9%, respectively). Based on the measured concentrations of parabens in marine fish samples, the estimated daily intake was calculated for children and adults with the corresponding values of 0.0477 µg/kg/day and 0.0119 µg/kg/day, respectively. However, the presence of parabens in Vietnamese marine fish may not pose a significant risk to human health.


Assuntos
Parabenos , Espectrometria de Massas em Tandem , Adulto , Criança , Animais , Humanos , Parabenos/análise , Peixes , Conservantes Farmacêuticos , Cromatografia Líquida de Alta Pressão/métodos , Solventes
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