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1.
J Immunother Cancer ; 12(6)2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-38910009

RESUMO

PURPOSE: This study aimed to investigate the prognostic significance of pretreatment dynamic contrast-enhanced (DCE)-MRI parameters concerning tumor response following induction immunochemotherapy and survival outcomes in patients with locally advanced non-small cell lung cancer (NSCLC) who underwent immunotherapy-based multimodal treatments. MATERIAL AND METHODS: Unresectable stage III NSCLC patients treated by induction immunochemotherapy, concurrent chemoradiotherapy (CCRT) with or without consolidative immunotherapy from two prospective clinical trials were screened. Using the two-compartment Extend Tofts model, the parameters including Ktrans, Kep, Ve, and Vp were calculated from DCE-MRI data. The apparent diffusion coefficient was calculated from diffusion-weighted-MRI data. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to assess the predictive performance of MRI parameters. The Cox regression model was used for univariate and multivariate analysis. RESULTS: 111 unresectable stage III NSCLC patients were enrolled. Patients received two cycles of induction immunochemotherapy and CCRT, with or without consolidative immunotherapy. With the median follow-up of 22.3 months, the median progression-free survival (PFS) and overall survival (OS) were 16.3 and 23.8 months. The multivariate analysis suggested that Eastern Cooperative Oncology Group score, TNM stage and the response to induction immunochemotherapy were significantly related to both PFS and OS. After induction immunochemotherapy, 67 patients (59.8%) achieved complete response or partial response and 44 patients (40.2%) had stable disease or progressive disease. The Ktrans of primary lung tumor before induction immunochemotherapy yielded the best performance in predicting the treatment response, with an AUC of 0.800. Patients were categorized into two groups: high-Ktrans group (n=67, Ktrans>164.3×10-3/min) and low-Ktrans group (n=44, Ktrans≤164.3×10-3/min) based on the ROC analysis. The high-Ktrans group had a significantly higher objective response rate than the low-Ktrans group (85.1% (57/67) vs 22.7% (10/44), p<0.001). The high-Ktrans group also presented better PFS (median: 21.1 vs 11.3 months, p=0.002) and OS (median: 34.3 vs 15.6 months, p=0.035) than the low-Ktrans group. CONCLUSIONS: Pretreatment Ktrans value emerged as a significant predictor of the early response to induction immunochemotherapy and survival outcomes in unresectable stage III NSCLC patients who underwent immunotherapy-based multimodal treatments. Elevated Ktrans values correlated positively with enhanced treatment response, leading to extended PFS and OS durations.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Quimiorradioterapia , Imunoterapia , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Masculino , Quimiorradioterapia/métodos , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Idoso , Imunoterapia/métodos , Adulto , Imageamento por Ressonância Magnética/métodos , Meios de Contraste , Resultado do Tratamento , Quimioterapia de Indução , Estadiamento de Neoplasias , Estudos Prospectivos
2.
Clin Cancer Res ; 30(13): 2719-2728, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38652815

RESUMO

PURPOSE: This phase I trial aimed to determine the maximum tolerated fraction dose (MTFD) of hypofractionated radiotherapy (hypo-RT) combined with concurrent chemotherapy and subsequent consolidation immune checkpoint inhibitors (cICI) for patients with locally advanced non-small cell lung cancer. PATIENTS AND METHODS: Split-course hypo-RT and hypoboost combined with concurrent chemotherapy was administered at three dose levels (DL), using a stepwise dose-escalation protocol. The sophisticated esophagus-sparing technique was implemented to restrict the dose to the esophagus. Patients who did not experience disease progression or unresolved ≥grade 2 (G2+) toxicities after RT received cICI. Each DL aimed to treat six patients. The MTFD was defined as the highest DL at which ≤2 patients of the six who were treated experienced treatment-related G3+ toxicity and ≤1 patient experienced G4+ toxicity within 12 months post-RT. RESULTS: Eighteen patients were enrolled, with six patients in each DL. All patients completed hypo-RT and concurrent chemotherapy, and 16 (88.9%) received at least one infusion of cICI, with a median of 10 infusions. Within the 12-month assessment period, one patient in DL1 experienced G3 pneumonitis, and one patient in DL3 developed G3 tracheobronchitis. The MTFD was not reached. The objective response rate was 100%. With a median follow-up of 20.9 months, the 1-year overall survival and progression-free survival rates were 94.4% and 83.3%, respectively. CONCLUSIONS: Utilizing the split-course hypo-RT and hypoboost approach, a fraction dose of 5 Gy to a total dose of 60 Gy, combined with concurrent chemotherapy and subsequent cICI, was well tolerated and yielded a promising objective response rate and survival outcomes.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Quimiorradioterapia , Neoplasias Pulmonares , Hipofracionamento da Dose de Radiação , Humanos , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Quimiorradioterapia/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dose Máxima Tolerável , Inibidores de Checkpoint Imunológico/administração & dosagem , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Adulto , Imunoterapia/métodos
3.
Appl Opt ; 63(10): 2601-2607, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38568542

RESUMO

Due to the presence of air turbulence in free-space optical (FSO) links, random fluctuations in wavefront phase and amplitude of the optical signal are reduced after it propagates through the air channel, which degrades the performance of free-space optical communication (FSOC) systems. Phase screen reflects the phase distortions resulting from air turbulence. Accordingly, accurate prediction with respect to phase screen is of significance for the FSOC. In this paper, we propose a phase screen prediction method based on the deep phase network (DPN). The advantages of the proposed method include strong robustness against air turbulence, low model depth, and fewer parameters as well as low complexity. The results reveal that our DPN enables desired inference accuracy and faster inference speed compared with the existing models, by combining the mean square deviation loss function with the pixel penalty terms. More concretely, the accuracy of phase screen prediction can reach up to 95%; further, the average time consumed to predict the phase screen is in the order of milliseconds only under various turbulence conditions. Also, our DPN outperforms the traditional Gerchberg-Saxton algorithm in convergence speed.

4.
Opt Express ; 32(5): 7243-7253, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38439410

RESUMO

Atmospheric coherence length is one of the most crucial parameters for free-space optical (FSO) links, which can reflect the level of phase and amplitude fluctuations caused by the atmospheric turbulence. In this paper, we study the evaluation of the atmospheric coherence length of the FSO links. The analytical expression of atmospheric coherence length is rendered based on the phase fluctuation resulting from atmospheric turbulence by using the most realistic Bump model. The proposed method is validated theoretically with the Monte Carlo phase screen. Also, the experimental setup with respect to FSO links is established with the spatial light modulator to validate the method experimentally, wherein the fluctuated phase is collected by Shack-Hartmann sensor. The results show that the evaluation of atmospheric coherence length by the analytical expression is consistent with the theoretical prediction as well as the experimental measurement. Thus, the proposed method enables the accurate evaluation of atmospheric coherence length under various turbulence conditions, which can assist the performance analysis as well as design of free-space optical communication systems.

7.
Radiat Res ; 201(1): 77-86, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38044712

RESUMO

Inflammatory response is one of the essential parts of various pathogenic mechanisms of radiation-induced salivary dysfunction. The effect of decreasing the levels of inflammatory cytokines on alleviating submandibular gland injuries after irradiation is unclear. This study aimed to explore the effect of the antibody against tumor necrosis factor-alpha, infliximab, on radiation-induced submandibular gland dysfunction in rats. Male Wistar rats received a single 20 Gy dose to the right submandibular gland region or sham irradiated. Meanwhile, the irradiated group was divided into infliximab treatment groups or untreated groups. Animals were euthanized at 1, 6, and 12 weeks postirradiation, and the irradiated submandibular gland was dissected for subsequent detection. Submandibular gland exposure caused obvious pathological changes. The increased levels of inflammatory cytokines, including tumor necrosis factor-alpha, interleukin-1ß, and interleukin-6, represent an aggravated inflammatory response. The results of the western blot, reverse transcription-quantitative polymerase chain reaction, and immunofluorescence staining showed upregulated levels of claudin-1, claudin-3, and aquaporin 5 and downregulated levels of claudin-4. Moreover, nuclear factor kappa-B phosphorylation levels were also up-regulated. In subsequent experiments, we found that infliximab alleviated inflammatory response, up-regulated tumor necrosis factor-alpha, interleukin-1ß, and interleukin-6 levels, and improved claudin-1, claudin-3, claudin-4, and aquaporin 5 expression. Our results indicate that infliximab might improve the para-cellular pathway and trans-cellular pathway destruction by reducing the inflammatory.


Assuntos
Glândula Submandibular , Fator de Necrose Tumoral alfa , Ratos , Masculino , Animais , Ratos Wistar , Infliximab/farmacologia , Infliximab/uso terapêutico , Infliximab/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Glândula Submandibular/metabolismo , Glândula Submandibular/patologia , Aquaporina 5/metabolismo , Claudina-3/metabolismo , Claudina-1/metabolismo , Claudina-4/metabolismo , Interleucina-1beta , Interleucina-6
8.
Cancer Med ; 12(17): 17638-17647, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37537968

RESUMO

PURPOSE: To determine the feasibility of incorporating bevacizumab consolidation into hypo-fractionated concurrent chemoradiotherapy (hypo-CCRT) for patients with unresectable locally advanced non-squamous non-small-cell lung cancer (LA-NS-NSCLC). PATIENTS AND METHODS: Eligible patients were treated with hypo-RT (40Gy in 10 fractions) followed by hypo-boost (24-28Gy in 6-7 fractions), along with concurrent weekly chemotherapy. Patients who completed the hypo-CCRT without experiencing ≥G2 toxicities received consolidation bevacizumab every 3 weeks for up to 1 year, until disease progression or unacceptable treatment-related toxicities. The primary endpoint was the risk of G4 or higher hemorrhage. Secondary endpoints included progression-free survival (PFS), overall survival (OS), locoregional failure-free survival (LRFS), distant metastasis-free survival (DMFS), and objective response rate (ORR). All time-to-event endpoints (OS, PFS, LRFS, and DMFS) were measured from the start of radiotherapy. RESULTS: Between December 2017 and July 2020, a total of 27 patients were included in the analysis, with a median follow-up duration of 28.0 months. One patient (3.7%) developed G5 hemorrhage during bevacizumab consolidation. Additionally, seven patients (25.9%) had G3 cough and three patients (11.1%) experienced G3 pneumonitis. The ORR for the entire cohort was 92.6%. The median OS was 37.0 months (95% confidence interval, 8.9-65.1 months), the median PFS was 16.0 months (95% confidence interval, 14.0-18.0 months), the median LRFS was not reached, and the median DMFS was 18.0 months. CONCLUSIONS: This pilot study met its goal of demonstrating the tolerability of consolidation bevacizumab after hypo-CCRT. Further investigation of antiangiogenic and immunotherapy combinations in LA-NSCLC is warranted, while the potential for grade 3 respiratory toxicities should be taken into consideration.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Bevacizumab/efeitos adversos , Neoplasias Pulmonares/patologia , Projetos Piloto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Estadiamento de Neoplasias , Quimiorradioterapia/efeitos adversos
9.
Cancer Med ; 12(14): 15000-15010, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37326436

RESUMO

BACKGROUND: We launched a single-arm phase II study to determine the efficacy and cost-effectiveness of percutaneous endoscopic gastrostomy (PEG) before concurrent chemoradiotherapy (CCRT) in patients with esophageal squamous cell carcinoma (ESCC). METHODS: Eligible patients received pretreatment PEG and enteral nutrition during CCRT. The primary outcome was the change of weight during CCRT. The secondary outcome included nutrition status, loco-regional objective response rate (ORR), loco-regional progression-free survival (LRFS), overall survival (OS), and toxicities. A 3-state Markov model was applied for cost-effectiveness analysis. Eligible patients were matched and compared with those who had nasogastric tube feeding (NTF) or oral nutritional supplements (ONS). RESULTS: Sixty-three eligible patients received pretreatment PEG-based CCRT. The mean change of weight during CCRT was -1.4% (standard deviation, 4.4%), and after CCRT, 28.6% of patients gained weight and 98.4% had normal albumin levels. The loco-regional ORR and 1-year LRFS were 98.4% and 88.3%. The incidence of grade ≥3 esophagitis was 14.3%. After matching, another 63 patients were included in the NTF group and 63 in the ONS group. More patients gained weight after CCRT in the PEG group (p = 0.001). The PEG group showed higher loco-regional ORR (p = 0.036) and longer 1-year LRFS (p = 0.030). In cost analysis, the PEG group showed an incremental cost-effectiveness ratio of $3457.65 per quality-adjusted life-years (QALY) compared with the ONS group with a probability of cost-effectiveness of 77.7% at the $10,000 per QALY willingness-to-pay threshold. CONCLUSION: Pretreatment PEG is associated with better nutritional status and treatment outcome in ESCC patients treated with CCRT compared with ONS and NTF. Pretreatment of PEG can be cost-effective because of its significant clinical benefits.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/patologia , Gastrostomia , Análise de Custo-Efetividade , Quimiorradioterapia/efeitos adversos , Estudos Retrospectivos
10.
Clin Transl Radiat Oncol ; 40: 100602, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36910023

RESUMO

Purpose: To assess the feasibility and potential benefits of online adaptive MR-guided fractionated stereotatic radiotherapy (FSRT) in patients with brain metastases (BMs). Methods and materials: Twenty-eight consecutive patients with BMs were treated with FSRT of 30 Gy in 5 fractions on the 1.5 T MR-Linac. The FSRT fractions employed daily MR scans and the contours were utilized to create each adapted plan. The brain lesions and perilesional edema were delineated on MR images of pre-treatment simulation (Fx0) and all fractions (Fx1, Fx2, Fx3, Fx4 and Fx5) to evaluate the inter-fractional changes. These changes were quantified using absolute/relative volume, Dice similarity coefficient (DSC) and Hausdorff distance (HD) metrics. Planning target volume (PTV) coverage and organ at risk (OAR) constraints were used to compare non-adaptive and adaptive plans. Results: A total of 28 patients with 88 lesions were evaluated, and 23 patients (23/28, 82.1%) had primary lung adenocarcinoma. Significant tumor volume reduction had been found during FSRT compared to Fx0 for all 88 lesions (median -0.75%, -5.33%, -9.32%, -17.96% and -27.73% at Fx1, Fx2, Fx3, Fx4 and Fx5, p < 0.05). There were 47 (47/88, 53.4%) lesions being accompanied by perilesional edema and the inter-fractional changes were significantly different compared to those without perilesional edema (p < 0.001). Patients with multiple lesions (13/28, 46.4%) had more significant inter-fractional tumor changes than those with single lesion (15/28, 53.6%), including tumor volume reduction and anatomical shift (p < 0.001). PTV coverage of non-adaptive plans was below the prescribed coverage in 26/140 fractions (19%), with 12 (9%) failing by more than 10%. All 140 adaptive fractions met prescribed target coverage. The adaptive plans also had lower dose to whole brain than non-adaptive plans (p < 0.001). Conclusions: Significant inter-fractional tumor changes could be found during FSRT in patients with BMs treated on the 1.5 T MR-Linac. Daily MR-guided re-optimization of treatment plans showed dosimetric benefit in patients with perilesional edema or multiple lesions.

11.
STOMATOLOGY ; (12): 176-181, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-979300

RESUMO

@#Tight junction(TJ) is complex dynamic system involved in protein interactions in the paracellular secretory pathway, with both barrier and fence functions. Claudin family, the main section of tight junction strands, will be abnormal in expression pattern in the circumstances of radiation injuries, inflammation, Sj?gren's syndrome, diabetes and other pathological conditions in salivary glands. This change leads to abnormal structure and function of tight junctions, indirectly manifested as salivary gland dysfunction. In addition, the difference of Claudin expression in salivary gland tumors can also be used as an indicator of tumor type and prognosis. This review focuses on the progress of research on common Claudin in salivary glands, including the structure, function, expression patterns of related diseases and their applications. It is believed that the review may provide new ideas for clinical and basic research on Claudin protein-related diseases.

12.
Gels ; 8(10)2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36286120

RESUMO

During the exploitation of deep and ultradeep oil and gas resources, the high-temperature problem of deep reservoirs has become a major challenge for water-based drilling fluids. In this study, a novel high-temperature-resistant filtrate reducer (LDMS) with low molecular weight was synthesized using N, N-dimethylacrylamide; sodium p-styrene sulfonate; and maleic anhydride, which can maintain the performance of a drilling fluid gel system under high temperature. Unlike the conventional high-temperature-resistant polymer filtrate reducer, LDMS does not significantly increase the viscosity and yield point of the drilling fluid gel systems. After aging at 210 °C, the filtrate volume of a drilling fluid with 2 wt% LDMS was only 8.0 mL. The mechanism of LDMS was studied by particle size distribution of a drilling fluid gel system, Zeta potential change, adsorption experiment, change of bentonite interlayer spacing, filter cake scanning electron microscope, and related theoretical analysis. The mechanism study revealed that LDMS could be adsorbed on the surface of bentonite particles in large quantities and intercalated into the interlayer of bentonite. Thus, it can improve the hydration degree of bentonite particles and the colloidal stability of the drilling fluid gel system, maintain the content of fine particles in the drilling fluid gel system, form a compact mud cake, and significantly reduce the filtrate volume of the drilling fluid gel system. Therefore, this work will promote the application of a low-molecular-weight polymer filtrate reducer in high-temperature-resistant water-based drilling fluid gel systems.

13.
Geospat Health ; 17(s1)2022 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-35829683

RESUMO

Although two years have passed since the coronavirus disease 2019 (COVID-19) outbreak, various variants are still rampant across the globe. The Omicron variant, in particular, is rapidly gained dominance through its ability to spread. In this study, we elucidated the spatial distribution pattern of Omicron from a global perspective. We used the cumulative number of notified COVID-19 cases per country spanning four weeks up to February 10, 2022, and the proportion of the Omicron variant genomic sequences from the Global Initiative on Sharing Avian Influenza Data (GISAID). The global spatial distribution of Omicron was investigated by analyzing Global & Local Moran's I and Getis- Ord General G. The spatial weight matrix was defined by combining K-Nearest neighbour and flight connectivity between countries. The results showed that the epidemic is relatively severe in Europe, countries with a high number of Omicron cases and incidence tended to be clustered spatially. In contrast, there are relatively fewer Omicron cases in Asia and Africa, with few hotspots identified. Furthermore, some noted spatial outliers, such as a lowvalue area surrounded by high-value areas, deserve special attention. This study has improved our awareness of the global distribution of Omicron. The findings can provide helpful information for deploying targeted epidemic preparedness for the subsequent COVID-19 variant and future epidemics.


Assuntos
COVID-19 , Animais , COVID-19/epidemiologia , Análise por Conglomerados , Humanos , Incidência , SARS-CoV-2
14.
Mol Pharm ; 19(2): 584-591, 2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-34982563

RESUMO

Medullary thyroid carcinoma (MTC) is a malignant neuroendocrine tumor with a high recurrence rate. Amyloid plaques formed from the misfolding of calcitonin are the key characteristics of MTC. Herein, we conducted a first-in-human pilot clinical study by applying a ß-amyloid-specific radiotracer, [18F]AV-45, to positron emission tomography (PET)/computed tomography (CT) imaging of MTC. The presence of amyloid plaques in the tumor tissue sections from five MTC patients was confirmed by hematoxylin and eosin (H&E) and Congo Red staining. [18F]AV-45 selectively accumulated in the amyloid plaques in the continued tumor tissue sections with similar distribution patterns to the H&E and Congo Red staining. In addition, the [18F]AV-45 uptake can be largely blocked by its nonradioactive reference compound. The [18F]AV-45 accumulation in the thyroid, neck lymph nodes, and muscles in healthy human subjects is close to the background indicated by PET/CT imaging. In the comparison PET/CT imaging study of a recurrent MTC patient, 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) showed an elevated uptake by multiple neck lymph nodes. In contrast, only one of these neck lymph nodes had increased [18F]AV-45 uptake. Postoperative histopathological analysis confirmed the [18F]AV-45 PET-positive lymph node as MTC with amyloid deposition, while other [18F]FDG positive lymph nodes were free from MTC and amyloid plaques. Thus, [18F]AV-45 showed the promise for the clinical PET/CT imaging of MTC.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Glândula Tireoide , Fluordesoxiglucose F18 , Humanos , Recidiva Local de Neoplasia , Tomografia por Emissão de Pósitrons/métodos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia
15.
Cleft Palate Craniofac J ; 59(8): 1024-1029, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34460333

RESUMO

OBJECTIVE: This study aimed to investigate the quality of life (QOL) of patients with cleft lip and palate and velopharyngeal insufficiency (VPI) in relation to sex, age, age at initial cleft lip surgery, and age at initial cleft palate surgery. DESIGN: This is a cross-sectional study. SETTING: The study was conducted in a tertiary medical center. PARTICIPANTS: The participants were caregivers of 72 patients with cleft lip and palate and VPI aged 4 to 20 years. MAIN OUTCOME MEASURE(S): Participants completed the Chinese version of the caregiver report of the VPI Effects on Life Outcomes (VELO) questionnaire. The Mann-Whitney U test was used to evaluate the patients' sex, age, age at initial cleft lip repair, and age at initial cleft palate repair in relation to VELO total score and domains. Spearman correlation analysis was completed including all study variables. Associations between the study variables and the VELO total score were tested using a generalized linear mixed model. RESULTS: In the univariate analysis, patients' age and age at initial cleft palate surgery influenced the QOL of patients with VPI. There were no differences in the VELO total score or domains based on sex or age at first cleft lip surgery. In the generalized linear mixed model, patients older than 8 years had higher VELO total scores. CONCLUSIONS: By caregiver report, the QOL of patients under age 8 years with VPI was lower than older patients. In addition, the caregiver impact domain was higher for parents of children who had their initial cleft palate surgery at age 2 years or younger.


Assuntos
Fenda Labial , Fissura Palatina , Insuficiência Velofaríngea , Criança , Pré-Escolar , China , Fenda Labial/cirurgia , Fissura Palatina/cirurgia , Estudos Transversais , Humanos , Qualidade de Vida , Resultado do Tratamento , Insuficiência Velofaríngea/cirurgia
16.
Front Immunol ; 13: 1054157, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36618425

RESUMO

Background: TMEM59L is a newly discovered transmembrane protein; its functions in cancer remain unknown. This study was designed to reveal the prognostic value and the functional role of TMEM59L in cancer. Methods: The gene expression profiles, methylation data, and corresponding clinical data of TMEM59L were retrieved from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression database. Survival analysis was employed to calculate the pan-cancer prognostic value of TMEM59L. The correlation between TMEM59L expression and tumor immune microenvironment, as well as DNA methylation dynamics and genomic heterogeneity across cancers were assessed based on data from TCGA. Results: Our findings revealed that distinct differences of TMEM59L mRNA expression were observed in different cancer types and that higher TMEM59L expression was observed in the advanced pathological stage and associated with worse prognosis in kidney renal papillary cell carcinoma, bladder urothelial carcinoma, colon adenocarcinoma, and kidney renal clear cell carcinoma. Pathway analysis indicated that TMEM59L exerted a key influence in cancer development and in immune- and cancer-associated pathways such as epithelial-mesenchymal transition and TGF-ß signaling. Moreover, correlation analysis hinted at a negative correlation of TMEM59L expression with CD8 T cells, activated CD4 T cells, and several immunomodulators, including IDO1, TIGIT, PD-L1, CTLA-4, and BTLA in various cancers. Survival analysis indicated that the hypermethylation of TMEM59L gene was associated with longer survival times. A significant correlation was also observed between TMEM59L expression and immunophenoscore, homologous recombination deficiency, loss of heterozygosity, tumor stemness score, and neoantigens in various cancers. Importantly, we also identified numerous potential agents that may target TMEM59L. Conclusion: Our study revealed the prognostic value as well as the genomic and immunological characteristics of TMEM59L in cancers, highlighting the promising potential for TMEM59L as a prognostic cancer biomarker and a therapeutic target.


Assuntos
Adenocarcinoma , Carcinoma de Células Renais , Carcinoma de Células de Transição , Neoplasias do Colo , Neoplasias Renais , Neoplasias da Bexiga Urinária , Humanos , Prognóstico , Genômica , Microambiente Tumoral/genética
18.
Ann Diagn Pathol ; 51: 151700, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33465722

RESUMO

Several studies revealed that non-small cell lung cancers (NSCLCs) frequently express ER, PR, HER2 and carry BRCA mutation. However, these markers in histological subtypes of lung adenocarcinoma have not been thoroughly investigated. We retrospectively evaluated a total of 640 lung adenocarcinoma samples for ERα, ERß, PR and HER2 expression by immunohistochemistry and western-blotting, for EGFR and BRCA mutation by real-time PCR and sequencing. Furthermore, HER2 amplification and mutation were explored in samples harboring immunopositivity HER2 using fluorescence in situ hybridization and real-time PCR, respectively. The micropapillary and invasive mucinous predominant adenocarcinoma were frequently detected the higher level of cytoplasmic ERß (64.9% and 56.6%), HER2 (68.1% and 60.1%) protein expression. But, amplification of HER2 was detected in only three cases (3/110, 2.7%) and 26 HER2 mutations in 110 cases were identified (23.6%) in the HER2 immunopositivity patients. Logistic regression analysis showed that cytoplasmic ERß (P = 0.032) and HER2 (P = 0.015) expression were independently associated with EGFR mutation. 8 patients (8/640, 1.25%) harbored pathogenic BRCA mutations, 6 with germline BRCA mutations and 2 with somatic BRCA1 mutations were detected with lacking ERß, PR and HER2 expression. Acinar predominant adenocarcinoma had the higher percentage of BRCA mutations than other subtypes. A systematic examination of ERß, HER2 and BRCA biomarkers could potentially be useful to diagnosis and identify patients with the histological subtypes of lung adenocarcinoma, who might benefit from the further individualized treatment of anti-hormone, anti-HER2 and/or PARP inhibitors therapeutics.


Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/genética , Receptor beta de Estrogênio/genética , Neoplasias Pulmonares/patologia , Receptor ErbB-2/genética , Adenocarcinoma de Pulmão/cirurgia , Proteína BRCA2/genética , Biomarcadores Tumorais/genética , Receptores ErbB/genética , Feminino , Histologia/instrumentação , Humanos , Imuno-Histoquímica/métodos , Hibridização in Situ Fluorescente/métodos , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias/métodos , Receptores de Progesterona/genética , Análise de Regressão , Estudos Retrospectivos , Ubiquitina-Proteína Ligases/genética
19.
Pathol Res Pract ; 216(8): 153037, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32703500

RESUMO

OBJECTIVE: The aim of this study was to evaluate the diagnostic value of detection of BRAF V600E mutation in the fine-needle aspiration cytology (FNAC) specimens of thyroid nodules and the relationship between BRAF V600E mutation and the clinicopathological characteristics of papillary thyroid carcinoma (PTC). METHODS: A total of 252 patients who underwent initial thyroid surgery were retrospectively analysed. All the patients underwent a preoperative FNAC at our institution, and the thyroid puncture cell fluid was used for both the cytological diagnosis and BRAF V600E mutational analysis using quantitative polymerase chain reaction. The Cochran-Mantel-Haenszel test was used to evaluate the diagnostic value of BRAF V600E mutation in FNAC fluid in diagnosing PTC. The association between BRAF V600E mutation and the clinicopathological parameters of PTC was analysed using the χ2 test. RESULTS: Through FNAC, 21 (8%), 60 (24%), and 171 (68%) cases were cytologically diagnosed as benign, indeterminate, and malignant, respectively. Postoperatively, 242 cases were histopathologically diagnosed as PTCs and 10 as goitre nodules. In the FNAC samples, 12 (57 %) of the 21 benign, 48 (80 %) of the 60 indeterminate, and 152 (88.9 %) of the 171 malignant cases showed BRAF V600E mutation. The histopathological diagnosis was used as the gold standard. The sensitivity and specificity of BRAF V600E mutational analysis in the FNAC samples for the diagnosis of PTC were 91.7 % and 100 % in benign, 82.8 % and 100 % in the indeterminate, and 89.4 % and 100 % in the malignant cases, respectively. CONCLUSION: BRAF V600E mutational analysis in FNAC samples of thyroid nodules can be used an effective supplementary diagnostic method at our institution. However, BRAF V600E mutation was not associated with aggressive characteristics in PTC.


Assuntos
Biomarcadores Tumorais/genética , Proteínas Proto-Oncogênicas B-raf/genética , Câncer Papilífero da Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Adulto , Biópsia por Agulha Fina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/terapia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/terapia
20.
BMC Med Imaging ; 20(1): 48, 2020 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375654

RESUMO

BACKGROUND: Localized biphasic MPeM is rare in clinical practice, we reviewed 8 cases of localized biphasic MPeM (including our present case), and summarized the clinical and imaging features of the disease. CASE PRESENTATION: We reported a 79-year-old man with chief complaint of a narrowing in the caliber of the stool for one year. A soft tissue shadow was occasionally found by CT examination in the right pelvic wall, and it was diagnosed as localized biphasic malignant peritoneal mesothelioma (MPeM) by postoperative pathology. Radical excision was performed and no radio-chemotherapy was applied. Nearly six years after surgery, the mass was significantly enlarged, and the neighboring tissues including rectum, prostate, seminal vesicle, and right ischial ramus were all infiltrated. The patient was in the end stage of cancer with poor prognosis. CONCLUSIONS: The localized biphasic MPeM may show following characteristics: (1) with heterogeneous low-density and obscure margin; (2) with low incidence rate of ascites; (3) with few central hemorrhage and necrosis; (4) with few calcified structures; (5) with mild to moderate heterogeneous delayed enhancement on contrast-enhanced CT. The imaging characteristics can provide further information for the diagnosis of localized biphasic MPeM in the future.


Assuntos
Mesotelioma Maligno/diagnóstico por imagem , Mesotelioma Maligno/cirurgia , Pelve/patologia , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Mesotelioma Maligno/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Pelve/diagnóstico por imagem , Neoplasias Peritoneais/patologia , Prognóstico , Tomografia Computadorizada por Raios X
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