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1.
Cancer Imaging ; 24(1): 61, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38741207

RESUMO

BACKGROUND: The value of postoperative radiotherapy (PORT) for patients with non-small cell lung cancer (NSCLC) remains controversial. A subset of patients may benefit from PORT. We aimed to identify patients with NSCLC who could benefit from PORT. METHODS: Patients from cohorts 1 and 2 with pathological Tany N2 M0 NSCLC were included, as well as patients with non-metastatic NSCLC from cohorts 3 to 6. The radiomic prognostic index (RPI) was developed using radiomic texture features extracted from the primary lung nodule in preoperative chest CT scans in cohort 1 and validated in other cohorts. We employed a least absolute shrinkage and selection operator-Cox regularisation model for data dimension reduction, feature selection, and the construction of the RPI. We created a lymph-radiomic prognostic index (LRPI) by combining RPI and positive lymph node number (PLN). We compared the outcomes of patients who received PORT against those who did not in the subgroups determined by the LRPI. RESULTS: In total, 228, 1003, 144, 422, 19, and 21 patients were eligible in cohorts 1-6. RPI predicted overall survival (OS) in all six cohorts: cohort 1 (HR = 2.31, 95% CI: 1.18-4.52), cohort 2 (HR = 1.64, 95% CI: 1.26-2.14), cohort 3 (HR = 2.53, 95% CI: 1.45-4.3), cohort 4 (HR = 1.24, 95% CI: 1.01-1.52), cohort 5 (HR = 2.56, 95% CI: 0.73-9.02), cohort 6 (HR = 2.30, 95% CI: 0.53-10.03). LRPI predicted OS (C-index: 0.68, 95% CI: 0.60-0.75) better than the pT stage (C-index: 0.57, 95% CI: 0.50-0.63), pT + PLN (C-index: 0.58, 95% CI: 0.46-0.70), and RPI (C-index: 0.65, 95% CI: 0.54-0.75). The LRPI was used to categorize individuals into three risk groups; patients in the moderate-risk group benefited from PORT (HR = 0.60, 95% CI: 0.40-0.91; p = 0.02), while patients in the low-risk and high-risk groups did not. CONCLUSIONS: We developed preoperative CT-based radiomic and lymph-radiomic prognostic indexes capable of predicting OS and the benefits of PORT for patients with NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Tomografia Computadorizada por Raios X , Humanos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/mortalidade , Masculino , Feminino , Tomografia Computadorizada por Raios X/métodos , Prognóstico , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Radioterapia Adjuvante/métodos , Radiômica
3.
Thorac Cancer ; 15(11): 938-943, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38426233

RESUMO

BACKGROUND: Consolidative thoracic radiotherapy (cTRT) has previously shown benefit to patients with extensive stage small cell lung cancer (ES-SCLC) who respond to chemotherapy. However, the optimum dose of cTRT is unknown. The purpose of this randomized trial is to compare the efficacy of 45 Gy in 15 fractions with 30 Gy in 10 fractions cTRT in ES-SCLC. METHODS: This phase III, multicenter, randomized trial is designed to evaluate the safety and efficacy of different cTRT dose in ES-SCLC. Eligible patients with pathologically confirmed ES-SCLC who responded to 4-6 cycles of etoposide plus cisplatin (EP) or carboplatin (EC) chemotherapy were randomized 1:1 to receive either 30 Gy in 10 fractions (standard dose) or 45 Gy in 15 fractions (high dose) cTRT. The primary endpoint is 2-year overall survival (OS). Secondary endpoints include 2-year progression-free survival (PFS), 2-year local control (LC) and treatment related toxicity as measured by adverse events according to the Common Terminology Criteria for Adverse Events (version 4.0). DISCUSSION: The present study is the first randomized phase III trial designed to evaluate the efficacy of higher versus lower dose cTRT in ES-SCLC, providing evidence for future clinical practice in prolonging survival of patients with ES-SCLC.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Cisplatino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Intervalo Livre de Progressão , Doses de Radiação , Etoposídeo , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto , Ensaios Clínicos Fase III como Assunto
4.
Mikrochim Acta ; 191(4): 202, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38492117

RESUMO

Chiral self-assembly is the spontaneous organization of individual building blocks from chiral (bio)molecules to macroscopic objects into ordered superstructures. Chiral self-assembly is ubiquitous in nature, such as DNA and proteins, which formed the foundation of biological structures. In addition to chiral (bio) molecules, chiral ordered superstructures constructed by self-assembly have also attracted much attention. Chiral self-assembly usually refers to the process of forming chiral aggregates in an ordered arrangement under various non-covalent bonding such as H-bond, π-π interactions, van der Waals forces (dipole-dipole, electrostatic effects, etc.), and hydrophobic interactions. Chiral assembly involves the spontaneous process, which followed the minimum energy rule. It is essentially an intermolecular interaction force. Self-assembled chiral materials based on chiral recognition in electrochemistry, chiral catalysis, optical sensing, chiral separation, etc. have a broad application potential with the research development of chiral materials in recent years.

5.
Radiother Oncol ; 196: 110261, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38548115

RESUMO

OBJECTIVE: Radiation pneumonitis (RP) is the major dose-limiting toxicity of thoracic radiotherapy. This study aimed to developed a dual-omics (single nucleotide polymorphisms, SNP and dosiomics) prediction model for symptomatic RP. MATERIALS AND METHODS: The potential SNPs, which are of significant difference between the RP grade ≥ 3 group and the RP grade ≤ 1 group, were selected from the whole exome sequencing SNPs using the Fisher's exact test. Patients with lung cancer who received thoracic radiotherapy at our institution from 2009 to 2016 were enrolled for SNP selection and model construction. The factorization machine (FM) method was used to model the SNP epistasis effect, and to construct the RP prediction model (SNP-FM). The dosiomics features were extracted, and further selected using the minimum redundancy maximum relevance (mRMR) method. The selected dosiomics features were added to the SNP-FM model to construct the dual-omics model. RESULTS: For SNP screening, peripheral blood samples of 28 patients with RP grade ≥ 3 and the matched 28 patients with RP grade ≤ 1 were sequenced. 81 SNPs were of significant difference (P < 0.015) and considered as potential SNPs. In addition, 21 radiation toxicity related SNPs were also included. For model construction, 400 eligible patients (including 108 RP grade ≥ 2) were enrolled. Single SNP showed no strong correlation with RP. On the other hand, the SNP-SNP interaction (epistasis effect) of 19 SNPs were modeled by the FM method, and achieved an area under the curve (AUC) of 0.76 in the testing group. In addition, 4 dosiomics features were selected and added to the model, and increased the AUC to 0.81. CONCLUSIONS: A novel dual-omics model by synergizing the SNP epistasis effect with dosiomics features was developed. The enhanced the RP prediction suggested its promising clinical utility in identifying the patients with severe RP during thoracic radiotherapy.

6.
J Pharm Anal ; 14(1): 1-15, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38352954

RESUMO

Esophageal cancer is an upper gastrointestinal malignancy with a bleak prognosis. It is still being explored in depth due to its complex molecular mechanisms of occurrence and development. Lipids play a crucial role in cells by participating in energy supply, biofilm formation, and signal transduction processes, and lipid metabolic reprogramming also constitutes a significant characteristic of malignant tumors. More and more studies have found esophageal cancer has obvious lipid metabolism abnormalities throughout its beginning, progress, and treatment resistance. The inhibition of tumor growth and the enhancement of antitumor therapy efficacy can be achieved through the regulation of lipid metabolism. Therefore, we reviewed and analyzed the research results and latest findings for lipid metabolism and associated analysis techniques in esophageal cancer, and comprehensively proved the value of lipid metabolic reprogramming in the evolution and treatment resistance of esophageal cancer, as well as its significance in exploring potential therapeutic targets and biomarkers.

7.
ACS Sens ; 9(2): 923-931, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38335470

RESUMO

The introduction of chirality into easy-scalable metal-organic frameworks (MOFs) gives rise to the development of advanced electrochemical sensors. However, integrating chirality by directly connecting metal ions and chiral ligands is unpredictable. Postmodification synthesis is a common method for synthesizing chiral MOFs, but it reduces the size of chiral channels and poses obstacles to the approach of chiral guest molecules. In this work, missing connection defects were introduced into the chiral MOFs through defect engineering strategies, which enhance the recognition of the target enantiomers. pH can tune enantioselectivity reversal in defective chiral MOFs. The chiral MOFs show enantioselectivity for d-Trp at pH = 5 and l-Trp at pH = 8. From the results of zeta potential, regardless of pH 5 or 8, the chiral MOF has a positive potential. The chiral MOFs are positively charged, while tryptophan is negatively charged when pH = 8. The difference in the positive and negative charge interactions between the two amino acids and chiral MOFs leads to chiral recognition. However, the difference in π-π interaction between chiral MOF and Trp enantiomers mainly drives chiral recognition under pH = 5. This study paves a pathway for the synthesis of defective chiral MOFs and highlights the pH-tuned enantioselectivity reversal.


Assuntos
Estruturas Metalorgânicas , Estruturas Metalorgânicas/química , Aminoácidos , Triptofano , Metais , Concentração de Íons de Hidrogênio
8.
Nanomedicine (Lond) ; 19(2): 127-143, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38131290

RESUMO

Background: Photodynamic therapy (PDT) of cancer has been limited by the poor solubility of most photosensitizers, use of high drug dosages, and the pH difference between the tumor tissue microenvironment (slightly acidic) and the bloodstream. These affect cellular uptake, selectivity and singlet oxygen generation. Materials & methods: We formulated Photinia glabra-green synthesized zinc oxide-protoporphyrin IX (PG-ZnO-PP) nanoconjugates by conjugating the ZnO nanoparticles enriched with amino groups and PP. Results: PG-ZnO-PP nanoconjugates showed higher rate of reactive oxygen species generation, improved cellular uptake in the acidic pH and lower IC50 toward Eca-109 cells for PDT. Conclusion: PG-ZnO-PP nanoconjugates are a potential solution to reducing drug dosage of PP through improved drug uptake, for enhanced targetability and reduced skin photosensitivity with improved PDT efficacy.


The progress of treating cancer using light-sensitive drugs and laser light of known wavelength has been limited by the poor solubility of most light-sensitive drugs, the use of high drug dosages and the slightly acidic environment within the cancerous tissues compared with normal blood in the body. These affect the ability of drugs to accumulate in cancerous cells, and not the normal cells, and the ability to produce the oxygen species that are toxic to the cancerous cells. In this paper, we prepared nanoparticles from zinc acetate using Photinia glabra (PG) fruit extract which were then used to chemically react with a light-sensitive drug called protoporphyrin IX (PP) to formulate small particles known as PG­zinc oxide (ZnO)­PP nanoconjugates. Our results showed that PG­ZnO­PP nanoconjugates had the ability to produce the toxic oxygen particles at a high rate and in good quantity. They also had a higher capability to accumulate in the cancerous cells at a pH below 7 with lower values of the drug needed to cause 50% of cell death toward the cancerous cells which affect the tube that connects from the throat to the stomach when projected with laser light. We could consider PG­ZnO­PP nanoconjugates to serve as a potential solution for reducing the dosage of PP needed to treat cancer in the presence of laser light, and at the same time they can help to reduce the skin-related side effects for patients after treatment when exposed to light.


Assuntos
Neoplasias , Photinia , Fotoquimioterapia , Protoporfirinas , Óxido de Zinco , Nanoconjugados , Óxidos , Fármacos Fotossensibilizantes/farmacologia , Linhagem Celular Tumoral , Concentração de Íons de Hidrogênio , Neoplasias/tratamento farmacológico
9.
Cancer Lett ; 582: 216569, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38101608

RESUMO

Progression occurs in approximately two-thirds of patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving chemoradiation and consolidation immunotherapy. Molecular indicators for outcome prediction are under development. A novel metric, the ratio of mean to max variant allele frequency (mmVAF), was derived from 431 pre-treatment tissue biopsies from The Cancer Genome Atlas and evaluated in serial circulating tumor DNA (ctDNA) from 70 LA-NSCLC patients receiving definitive radiotherapy/chemoradiotherapy (RT/CRT) with/without immunotherapy. High mmVAFs in pre-treatment tissue biopsies, indicating clonal predominant tumors (P < 0.01), were associated with inferior overall survival [OS, hazard ratio (HR): 1.48, 95 % confidence interval (CI): 1.11-1.98]. Similar associations of mmVAF with clonality (P < 0.01) and OS (HR: 2.24, 95 % CI: 0.71-7.08) were observed in pre-treatment ctDNA. At 1-month post-RT, ctDNA mmVAF-high patients receiving consolidation immunotherapy exhibited improved progression-free survival (PFS) compared to those who did not (HR: 0.14, 95 % CI: 0.03-0.67). From the baseline to week 4 of RT and/or 1-month post-RT, survival benefits from consolidation immunotherapy were exclusively observed in ctDNA mmVAF-increased patients (PFS, HR: 0.39, 95 % CI: 0.14-1.15), especially in terms of distant metastasis (HR: 0.11, 95 % CI: 0.01-0.95). In summary, our longitudinal data demonstrated the applicability of ctDNA-defined clonality for prognostic stratification and immunotherapy benefit prediction in LA-NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/tratamento farmacológico , Prognóstico , Quimiorradioterapia , Imunoterapia
10.
Thorac Cancer ; 14(28): 2839-2845, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37596813

RESUMO

BACKGROUND: Radiotherapy-induced esophagitis (RE) diminishes the quality of life and interrupts treatment in patients with non-small cell lung cancer (NSCLC) undergoing postoperative radiotherapy. Dosimetric models showed limited capability in predicting RE. We aimed to develop dosiomic models to predict RE. METHODS: Models were trained with a real-world cohort and validated with PORT-C randomized controlled trial cohort. Patients with NSCLC undergoing resection followed by postoperative radiotherapy between 2004 and 2015 were enrolled. The endpoint was grade ≥2 RE. Esophageal three-dimensional dose distribution features were extracted using handcrafted and convolutional neural network (CNN) methods, screened using an entropy-based method, and selected using minimum redundancy and maximum relevance. Prediction models were built using logistic regression. The areas under the receiver operating characteristic curve (AUC) and precision-recall curve were used to evaluate prediction model performance. A dosimetric model was built for comparison. RESULTS: A total of 190 and 103 patients were enrolled in the training and validation sets, respectively. Using handcrafted and CNN methods, 107 and 4096 features were derived, respectively. Three handcrafted, four CNN-extracted and three dosimetric features were selected. AUCs of training and validation sets were 0.737 and 0.655 for the dosimetric features, 0.730 and 0.724 for handcrafted features, and 0.812 and 0.785 for CNN-extracted features, respectively. Precision-recall curves revealed that CNN-extracted features outperformed dosimetric and handcrafted features. CONCLUSIONS: Prediction models may identify patients at high risk of developing RE. Dosiomic models outperformed the dosimetric-feature model in predicting RE. CNN-extracted features were more predictive but less interpretable than handcrafted features.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Esofagite , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Qualidade de Vida , Modelos Logísticos
11.
Adv Radiat Oncol ; 8(4): 101213, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37152488

RESUMO

Purpose: Cardiopulmonary toxic effects may reduce the efficacy of postoperative radiation therapy (PORT) in patients with non-small cell lung cancer (NSCLC). However, few studies have examined whether the heart and lung doses affect overall survival (OS). We investigated the correlation of heart and lung doses with OS in patients with NSCLC undergoing PORT. Methods and Materials: This retrospective analysis included 307 patients with NSCLC undergoing PORT. The total dose was 50 Gy. Landmark analyses were performed at 36 months, with hazard ratios (HRs) calculated separately for events occurring up to 36 months (early survival) and after 36 months (long-term survival). Stabilized inverse probability of treatment weighting (sIPTW) was performed to balance the characteristics of the high- and low-dose groups. We performed sensitivity analyses at 24 and 48 months. Results: The median follow-up period was 67.42 months. Heart doses were significantly correlated with long-term survival (HR, 1.14; P = .015) but not with early survival (HR, 0.97; P = .41) or whole survival (HR, 1.02; P = .58). Lung doses were marginally significantly correlated with early survival (HR, 1.03; P = .07) but not with long-term survival (HR, 1.00; P = .85) or whole survival (HR, 1.02; P = .12). Higher heart and lung doses were associated with decreased long-term and early survival, respectively, before and after sIPTW. Landmark analyses at 24 and 48 months showed consistent results. Conclusions: For patients with NSCLC undergoing PORT, a higher heart dose was associated with decreased long-term survival, whereas a higher lung dose was associated with decreased early survival.

13.
J Colloid Interface Sci ; 642: 648-657, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37030201

RESUMO

Conjugated microporous polymers (CMPs) have been considered a type of promising visible-light-driven, organic photocatalysts. However, apart from designing high-performance CMPs from a molecular perspective, little attention is paid to improving the photocatalytic properties of these polymers through macrostructural regulation. Herein, we prepared a kind of hollow spherical CMPs involving carbazole monomers and studied their performance on the selective photocatalytic oxidation of benzyl alcohol under visible light irradiation. The results demonstrate that the introduction of a hollow spherical structure improves the physicochemical properties of the as-designed CMPs, including the specific surface areas, optoelectronic characteristics, as well as photocatalytic performance, etc. In particular, the hollow CMPs can more effectively oxidize benzyl alcohol compared to pristine ones under blue light illumination, and produce >1 mmol of benzaldehyde in 4.5 h with a yield of up to 9 mmol·g-1·h-1, which is almost 5 times higher than that of the pristine ones. Furthermore, such hollow architecture has a similar enhanced effect on the oxidation of some other aromatic alcohols. This work shows that the deliberate construction of specific macrostructures can better arouse the photocatalytic activity of the as-designed CMPs, which will contribute to the further use of these organic polymer semiconductors in photocatalysis areas.

14.
Cancers (Basel) ; 15(5)2023 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-36900279

RESUMO

The aim of the current study is to evaluate the effect of segmental abutting esophagus-sparing (SAES) radiotherapy on reducing severe acute esophagitis in patients with limited-stage small-cell lung cancer treated with concurrent chemoradiotherapy. Thirty patients were enrolled from the experimental arm (45 Gy in 3 Gy daily fractions in 3 weeks) of an ongoing phase III trial (NCT02688036). The whole esophagus was divided into the involved esophagus and the abutting esophagus (AE) according to the distance from the edge of the clinical target volume. All dosimetric parameters were significantly reduced for the whole esophagus and AE. The maximal and mean doses of the esophagus (47.4 ± 1.9 Gy and 13.5 ± 5.8 Gy, respectively) and AE (42.9 ± 2.3 Gy and 8.6 ± 3.6 Gy, respectively) in the SAES plan were significantly lower than those (esophagus 48.0 ± 1.9 Gy and 14.7± 6.1 Gy, AE 45.1 ± 2.4 Gy and 9.8 ± 4.2 Gy, respectively) in the non-SAES plan. With a median follow-up of 12.5 months, only one patient (3.3%) developed grade 3 acute esophagitis, and no grade 4-5 events happened. SAES radiotherapy has significant dosimetric advantages, which are successfully translated into clinical benefits and provide good feasibility for dose escalation to improve local control and prognosis in the future.

15.
J Oncol ; 2023: 3591758, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36824664

RESUMO

Objectives: Indoleamine 2,3-dioxygenase 1 (IDO1) acts as the key rate-limiting enzyme that converts tryptophan (Trp) to kynurenine (Kyn). Its activity was primarily induced by interferon-γ (IFN-γ), which was reported to play a role in the development of acute radiation-induced pneumonitis. In this study, we aimed to investigate the correlation between IDO1 activity and radiation-induced lung toxicity (RILT) in stage III nonsmall cell lung cancer (NSCLC) patients who were treated with chemoradiotherapy (CRT). Materials and Methods: Systemic IDO1 activity was reflected by Kyn : Trp ratio. Plasma levels of Kyn and Trp in 113 stage III NSCLC patients were measured by high-performance liquid chromatography (HPLC) before the initiation of radiotherapy. Dynamic change of IDO1 activity was followed in 23 patients before, during, and after radiotherapy. We also used RNA sequencing (RNA-seq) data from the Cancer Genome Atlas Program (TCGA) database and performed gene set enrichment analysis (GSEA) to explore how IDO1 was involved in the development of RILT. Results: 9.7% (11/113) of the whole group developed G3+ (greater than or equal to Grade 3) RILT. Preradiation IDO1 activity was significantly higher in patients who developed G3 + RILT than in nonG3 + RILT patients. (P = 0.029, AUC = 0.70). Univariate and multivariate analyses showed that high IDO1 activity was independently associated with the risk of G3 + RILT (P = 0.034). A predictive model combining both IDO1 activity and FEV1 was established for severe RILT and displayed a moderate predictive value (AUC = 0.83, P < 0.001). The incidence of G3 + RILT was 2.6% (1/38) in patients with an IDO activity ≤0.069 and FEV1 > 59.4%, and 50.0% (6/12) in those with an IDO activity >0.069 and FEV1 ≤ 59.4%. Of 23 patients with dynamic tracking, the IDO1 activity of postradiation was significantly lower than midradiation (P = 0.021), though no significant differences among the three time points were observed (P = 0.070). Bioinformatic analysis using RNA-seq data from 1014 NSCLC patients revealed that IDO mainly functioned in the inflammatory response instead of the late fibrosis process in NSCLC patients. Conclusion: High baseline IDO1 activity combined with unfavorable baseline FEV1 was predictive of severe RILT in unresectable stage III NSCLC patients. IDO1 might play a role in the acute inflammatory response. Finding effective interventions to alleviate RILT using IDO inhibitors is warranted in the future.

16.
Front Immunol ; 14: 1341584, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38288117

RESUMO

Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape for locally advanced non-small-cell lung cancer (LA-NSCLC), whereas responses to anti-programmed cell death-1 (PD-1) or anti-programmed death-ligand 1 (PD-L1) are heterogeneous. Though consolidation ICI following concurrent chemoradiotherapy (cCRT) improves survival of NSCLC, this regimen is challenging for patients with bulky tumors due to excessive target volumes and radiation-resistant hypoxia during upfront cCRT, leading to higher risk of pneumonitis and inferior local-regional control. Recent trials have demonstrated neoadjuvant ICI brought greater benefit to stage III than stage I-II NSCLC. Our previous study also supported the therapeutic advantage of 2-cycle induction ICI for patients with bulky unresectable stage III NSCLC. In the context of induction immunotherapy, radiotherapy is more likely to exert immune synergistic effects, reverse anti-PD-1 resistance, and activate abscopal immune responses. Prospective trials to determine the efficacy and safety of induction ICI for bulky LA-NSCLC are necessary. Methods: This randomized, open-label, two-arm phase II study aims to explore whether 2 cycles of induction anti-PD-1 toripalimab plus chemotherapy can improve progression-free survival (PFS) in bulky LA-NSCLC. Bulky tumors are defined as primary lesion ≥5 cm in greatest dimension or metastatic lymph nodes ≥2 cm in shortest diameter. A total of 50 patients with bulky unresectable stage III NSCLC will be recruited and 1:1 randomized into the experimental arm: 2-cycle induction PD-1 inhibitor toripalimab plus chemotherapy followed by cCRT and consolidation toripalimab; or control arm: 2-cycle induction chemotherapy followed by cCRT and consolidation toripalimab. Patients are stratified by pathology (squamous versus non-squamous). The primary endpoint is PFS. Secondary endpoints are overall survival, overall response rate, disease control rate, duration of response, and incidence of adverse events. Exploratory analyses include PD-L1 expression and liquid biopsy-based biomarker testing, tumor microenvironment profiling at single-cell levels, and quality-of-life assessments. Discussion: The InTRist study is the first randomized phase II trial to investigate the feasibility of induction anti-PD-1 toripalimab plus chemotherapy followed by cCRT and consolidation toripalimab in bulky LA-NSCLC, providing novel evidence for the synergistic strategy combining anti-PD-1 blockade with radiotherapy to prolong immunotherapy benefits, overcome resistance, and enhance abscopal immune response. Clinical trial registration: ClinicalTrials.gov, identifier NCT05888402.


Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Antígeno B7-H1 , Estudos Prospectivos , Quimiorradioterapia/métodos , Microambiente Tumoral , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
ACS Appl Mater Interfaces ; 14(50): 56156-56168, 2022 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-36508197

RESUMO

As the power density of electronic devices continuously increases, there is a growing demand to improve the heat conduction performance of thermal management materials for addressing heat dissipation issues. Single-/few-layer graphene is a promising candidate as a filler of a metal matrix due to its extremely high thermal conductivity (k); however, the well-arranged assembly of 2D-component graphene with a high volume fraction remains challenging. Herein, we integrated a novel graphene-based macroscopic material of graphene film (GF) into a Cu matrix by infiltrating molten Zr-microalloyed Cu into a spirally folded and upright-standing GFs skeleton. The microstructure of the GF/Cu composites was regulated by an interface modification strategy. The GF/Cu composites with a spirally layered microstructure exhibit a superior k of 820 W/m K in the axial direction, much higher than that of Cu-matrix composites reinforced with graphene nanosheets (generally <500 W/m K) and twice that of Cu. The thermal transfer mechanisms were investigated by experiments and theoretical calculations. The results reveal that the excellent performance is attributed to the construction of high-heat conduction channels and a positive coordinating effect at the Zr-modified GF/Cu interface. Meanwhile, the relation between interfacial microstructure and heat transfer is established in the composites using interfacial thermal resistance as a bridge. This work yields in-depth insight into the heat conduction mechanism in highly oriented structures and provides a promising solution for the thermal management issues of high-power electronics.

18.
Nanoscale ; 14(46): 17466, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36398562

RESUMO

Correction for 'Enhanced energy harvester performance by a tension annealed carbon nanotube yarn at extreme temperatures' by Xinghao Hu et al., Nanoscale, 2022, 14, 16185-16192, https://doi.org/10.1039/D2NR05303A.

19.
Nanoscale ; 14(43): 16185-16192, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36278850

RESUMO

Carbon nanotube (CNT) yarns generate electrical energy when they were stretched in an electrolyte, and they have been exploited for diverse applications such as self-powered sensors and human health monitoring systems. Here we improved the capacitance change and harvester performance of a coiled CNT yarn by using an incandescent tension annealing process (ITAP). When undergoing stretching cycles at 1 Hz, a coiled ITAP yarn can produce 2.5 times peak electrical power and 1.6 times output voltage than that of a neat CNT yarn. Electrochemical analysis shows that the capacitance of the ITAP yarn decreased by 20.4% when it was stretched to 30% strain. Microstructure results demonstrate that the large capacitance change may result from the densified electrochemical surface by the ITAP. Moreover, the potential of the zero charge (PZC) of ITAP yarns was shifted to a more negative value than that of the neat CNT yarn, which means that more charges were injected into the ITAP yarn once it was immersed in an electrolyte. Thus, the large capacitance change and initial injected charge are two main reasons for enhancing the harvester performance of the ITAP yarn. In addition, by annealing a twisted CNT yarn before it was coiled, we further increased the output peak power density to 170 W kg-1 at a strain of 55%.

20.
Medicine (Baltimore) ; 101(42): e31215, 2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36281080

RESUMO

Esophageal carcinosarcoma is a rare type of esophageal cancer; however, few studies have investigated the effects of radiotherapy in locally advanced patients. This study aimed to report experience of the safety and efficacy of intensity-modulated radiotherapy for locally advanced esophageal carcinosarcoma and review the literature. By searching the institutional database between January 2010 and December 2020, along with the literature review, 25 patients were eligible for the study. The clinical and radiologic information of all patients with esophageal carcinosarcoma who underwent radiotherapy were collected. Survival outcomes were calculated using Kaplan-Meier plots. In our series, 5 patients were in the curative/neoadjuvant radiotherapy group and 10 patients were in the adjuvant group. Most tumors were protruding (n = 10, 66.7%). All patients underwent intensity-modulated radiotherapy. In the curative/neoadjuvant radiotherapy group, 2 patients underwent concurrent chemoradiotherapy before surgery, and the other three received radiotherapy alone as the initial treatment. The median follow-up time was 43.1 months. All patients showed a partial response at the efficacy evaluation. The median time of overall survival and progression-free survival were 40.2 months (95% confidence interval [CI], 13.1-67.3 months) and 19.0 months (95% CI, 13.9 months-24.1 months) for the entire cohort, but were not reached for curative/neoadjuvant radiotherapy group. Overall survival (hazard ratio [HR] 0.81, 95% CI, 0.15-4.43; P = .805) and progression-free survival (HR 1.68, 95% CI, 0.35-8.19; P = .514) did not differ significantly between the 2 groups. When considering the literature review data in the final analysis, overall survival (HR 0.84, 95% CI, 0.25-2.81; P = .779) and progression-free survival (HR, 0.68; 95% CI, 0.26-1.76; P = .425) were also not different between the 2 groups. Treatment based on intensity-modulated radiotherapy with neoadjuvant or curative intent may be an option for patients with unresectable esophageal carcinosarcoma. Further research with a larger sample size is needed to validate the reliability.


Assuntos
Carcinossarcoma , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Radioterapia de Intensidade Modulada , Humanos , Intervalo Livre de Doença , Reprodutibilidade dos Testes , Neoplasias Esofágicas/patologia , Carcinossarcoma/radioterapia
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