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1.
Oncologist ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34472667

RESUMO

BACKGROUND: In early trials, hypersensitivity reactions (HSRs) to paclitaxel were common, thus prompting the administration of antihistamines and corticosteroids before every paclitaxel dose. We tested the safety of omitting corticosteroids after cycle 2 during the paclitaxel portion of the dose-dense (DD) doxorubicin-cyclophosphamide (AC)-paclitaxel regimen. PATIENTS, MATERIALS, AND METHODS: In this prospective, single-arm study, patients who completed four cycles of DD-AC for stage I-III breast cancer received paclitaxel 175 mg/m2 every 2 weeks for four cycles. Patients received a standard premedication protocol containing dexamethasone, diphenhydramine, and a histamine H2 blocker prior to the first two paclitaxel cycles. Dexamethasone was omitted in cycles three and four if there were no HSRs in previous cycles. We estimated the rate of grade 3-4 HSRs. RESULTS: Among 127 patients enrolled, 125 received more than one dose of protocol therapy and are included in the analysis. Fourteen (11.2%; 90% confidence interval, 6.9%-20.0%) patients had any-grade HSRs, for a total of 22 (4.5%; 3.1%-6.4%) HSRs over 486 paclitaxel cycles. Any-grade HSRs occurred in 1.6% (0.3%-5.0%), 6.5% (3.3%-11.3%), 7.4% (3.9%-12.5%), and 2.6% (0.7%-6.6%) of patients after paclitaxel cycles 1, 2, 3, and 4, respectively. Dexamethasone use was decreased by 92.8% in cycles 3 and 4. Only one patient experienced grade 3 HSR in cycles 3 or 4, for a rate of grade 3/4 HSR 0.4% (0.02%-2.0%) (1/237 paclitaxel infusions). That patient had grade 2 HSR during cycle 2, and the subsequent grade 3 event occurred despite usual dexamethasone premedication. A sensitivity analysis restricted to patients not known to have received dexamethasone in cycles 3 and 4 found that any-grade HSRs occurred in 2.7% (3/111; 0.7%-6.8%) and 0.9% (1/109; 0.05%-4.3%) of patients in cycle 3 and 4, respectively. CONCLUSION: Corticosteroid premedication can be safely omitted in cycles 3 and 4 of dose-dense paclitaxel if HSRs are not observed during cycles 1 and 2. IMPLICATIONS FOR PRACTICE: Because of the potential for hypersensitivity reactions (HSRs) to paclitaxel, corticosteroids are routinely prescribed prior to each dose, on an indefinite basis. This prospective study, including 125 patients treated with 486 paclitaxel cycles, demonstrates that corticosteroids can be safely omitted in future cycles if HSRs did not occur during cycles 1 and 2 of paclitaxel and that this strategy reduces the use of corticosteroids in cycles 3 and 4 by 92.8% relative to current standard of care.

2.
Nat Commun ; 12(1): 5563, 2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34548479

RESUMO

Immune checkpoint inhibitors (ICIs) have minimal therapeutic effect in hormone receptor-positive (HR+ ) breast cancer. We present final overall survival (OS) results (n = 88) from a randomized phase 2 trial of eribulin ± pembrolizumab for patients with metastatic HR+ breast cancer, computationally dissect genomic and/or transcriptomic data from pre-treatment tumors (n = 52) for molecular associations with efficacy, and identify cytokine changes differentiating response and ICI-related toxicity (n = 58). Despite no improvement in OS with combination therapy (hazard ratio 0.95, 95% CI 0.59-1.55, p = 0.84), immune infiltration and antigen presentation distinguished responding tumors, while tumor heterogeneity and estrogen signaling independently associated with resistance. Moreover, patients with ICI-related toxicity had lower levels of immunoregulatory cytokines. Broadly, we establish a framework for ICI response in HR+ breast cancer that warrants diagnostic and therapeutic validation. ClinicalTrials.gov Registration: NCT03051659.

3.
J Hazard Mater ; 424(Pt A): 127283, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34564045

RESUMO

Microplastics (MPs) pollution is increasingly appreciated as a significant environmental issue, however, the large-scale pattern of MPs in farmland soils and its associated environmental impacts are unknown. This study investigated a national-scale distribution of micro(meso)plastics (MMPs) in the soil of 30 farmlands across China. The abundance of MMPs in soils was 25.56-2067.78 items kg-1, with a mean of 358.37 items kg-1, i.e. 6.79 mg kg-1 or 0.0007% after mass conversion. MPs accounted for 93.1% of MMPs, the abundance varied greatly among different regions, high in arid or semi-arid north but relatively low in mild southwest regions. Major MPs included polypropylene, polyethylene, and polyester, tending to decrease in abundance from surface to deeper soil layers. Further, meta-analysis revealed that MPs exposure influenced bulk density, soil enzymes including fluorescein diacetate hydrolase (FDAse) and urease, and crop biomass, and minimum effective concentrations (MEC) were in the range of 0.0040-10%. We found that actual abundance in the national-scale soils was lower than MEC, but partly overlapped or close, which implies various degrees of environmental impacts. These findings disclose the national-scale pollution pattern of MPs in farmlands and its latent risks to soil environments and crop growth.

4.
JAMA Surg ; 156(10): e213758, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34468718

RESUMO

Importance: Increasing rates of bilateral mastectomy have been most pronounced in young women with breast cancer, but the association of surgery with long-term quality of life (QOL) remains largely unknown. Objective: To examine the association of surgery with longer-term satisfaction and QOL in young breast cancer survivors. Design, Setting, and Participants: This multicenter cross-sectional study of a prospective cohort was conducted from October 2016 to November 2017, at academic and community hospitals in North America. Women 40 years or younger enrolled in the Young Women's Breast Cancer Study were assessed. Data analysis was performed from during a 1- to 2-year period after conclusion of the study. Exposures: Primary breast surgery, reconstruction, and radiotherapy. Main Outcomes and Measures: Mean BREAST-Q breast satisfaction and physical, psychosocial, and sexual well-being scores were compared by type of surgery; higher BREAST-Q scores (range, 0-100) indicate better QOL. Linear regression was used to identify demographic and clinical factors associated with BREAST-Q scores for each domain. Results: A total of 560 women with stage 0 to III breast cancer (median age at diagnosis, 36 years; range, 17-40 years; 484 [86%] with stage 0-II disease) completed the BREAST-Q a median of 5.8 years (range, 1.9-10.4 years) from diagnosis. A total of 290 patients (52%) of patients underwent bilateral mastectomy, 110 patients (20%) underwent unilateral mastectomy, and 160 patients (28%) received breast-conserving therapy. Among mastectomy patients, 357 (89%) had reconstruction and 181 (45%) received radiotherapy. In multivariate analyses, implant-based reconstruction (vs autologous) was associated with decreased breast satisfaction (ß = -7.4; 95% CI, -12.8 to -2.1; P = .007) and complex reconstruction (vs autologous) with worse physical well-being (ß = -14.0; 95% CI, -22.2 to -5.7; P < .001). Conclusions and Relevance: These results suggest that local therapy in young breast cancer survivors is persistently associated with poorer scores in multiple QOL domains, particularly among those treated with mastectomy and radiotherapy, irrespective of breast reconstruction. Socioeconomic stressors also appear to play a role.

5.
Clin Cancer Res ; 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376536

RESUMO

PURPOSE: Programmed cell death receptor-1 (PD-1) inhibitors are frontline therapy in advanced melanoma. Severe immune-related adverse effects (irAEs) often require immunosuppressive treatment with glucocorticoids (GCCs), but GCC use and its correlation with patient survival outcomes during anti-PD-1 monotherapy remains unclear. EXPERIMENTAL DESIGN: In this multicenter retrospective analysis, patients treated with anti-PD-1 monotherapy between 2009 and 2019 and detailed GCC use, data were identified from five independent cohorts, with median follow-up time of 206 weeks. IrAEs were tracked from the initiation of anti-PD-1 until disease progression, initiation of a new therapy, or last follow-up. Correlations between irAEs, GCC use, and survival outcomes were analyzed. RESULTS: Of the entire cohort of 947 patients, 509 (54%) developed irAEs. In the MGH cohort [irAE(+) n = 90], early-onset irAE (within 8 weeks of anti-PD-1 initiation) with high-dose GCC use (≥60-mg prednisone equivalent once a day) was independently associated with poorer post-irAE PFS/OS (progression-free survival/overall survival) [post-irAE PFS: HR, 5.37; 95% confidence interval (CI), 2.10-13.70; P < 0.001; post-irAE OS: HR, 5.95; 95% CI, 2.20-16.09; P < 0.001] compared with irAEs without early high-dose GCC use. These findings were validated in the combined validation cohort [irAE(+) n = 419, post-irAE PFS: HR, 1.69; 95% CI, 1.04-2.76; P = 0.04; post-irAE OS: HR, 1.97; 95% CI, 1.15-3.39; P = 0.01]. Similar findings were also observed in the 26-week landmark analysis for post-irAE-PFS but not for post-irAE-OS. A sensitivity analysis using accumulated GCC exposure as the measurement achieved similar results. CONCLUSIONS: Early high-dose GCC use was associated with poorer PFS and OS after irAE onset. Judicious use of GCC early during anti-PD-1 monotherapy should be considered. Further prospective randomized control clinical trials designed to explore alternative irAE management options are warranted.

6.
Molecules ; 26(16)2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34443530

RESUMO

Ageing-related bone impairment due to exposure to hyperglycemic environment is scarcely researched. The aim was to confirm the improvement effects of undenatured type II collagen (UC II) on bone impairment in ageing db/db mice, and the ageing model was established by normal feeding for 48-week-old. Then, the ageing db/db mice were randomly assigned to UC II intervention, the ageing model, and the chondroitin sulfate + glucosamine hydrochloride control groups. After 12 weeks of treatment, femoral microarchitecture and biomechanical parameters were observed, biomarkers including bone metabolism, inflammatory cytokines, and oxidative stress were measured, and the gastrocnemius function and expressions of interleukin (IL) 1ß, receptor activator of nuclear factor (NF)-κB ligand (RANKL), and tartrate-resistant acid phosphatase (TRAP) were analyzed. The results showed that the mice in the UC II intervention group showed significantly superior bone and gastrocnemius properties than those in the ageing model group, including bone mineral density (287.65 ± 72.77 vs. 186.97 ± 32.2 mg/cm3), gastrocnemius index (0.46 ± 0.07 vs. 0.18 ± 0.01%), muscle fiber diameter (0.0415 ± 0.005 vs. 0.0330 ± 0.002 mm), and cross-sectional area (0.0011 ± 0.00007 vs. 0.00038 ± 0.00004 mm2). The UC II intervention elevated bone mineralization and formation and decreased bone resorption, inflammatory cytokines, and the oxidative stress. In addition, lower protein expression of IL-1ß, RANKL, and TRAP in the UC II intervention group was observed. These findings suggested that UC II improved bones impaired by T2DM during ageing, and the likely mechanism was partly due to inhibition of inflammation and oxidative stress.


Assuntos
Reabsorção Óssea/tratamento farmacológico , Colágeno Tipo II/farmacologia , Interleucina-1beta/genética , Ligante RANK/genética , Fosfatase Ácida Resistente a Tartarato/genética , Envelhecimento/efeitos dos fármacos , Envelhecimento/genética , Envelhecimento/patologia , Animais , Densidade Óssea/efeitos dos fármacos , Reabsorção Óssea/etiologia , Reabsorção Óssea/genética , Reabsorção Óssea/patologia , Sulfatos de Condroitina/farmacologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Glucosamina/farmacologia , Humanos , Inflamação/tratamento farmacológico , Inflamação/etiologia , Inflamação/genética , Inflamação/patologia , Camundongos , Camundongos Endogâmicos NOD/genética , Estresse Oxidativo/efeitos dos fármacos
7.
Nutrients ; 13(6)2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34204516

RESUMO

Peptic ulcer has a serious impact on people's health around the world, and traditional medicines can cause adverse reactions. This study investigated the protective effects of tilapia collagen oligopeptides (TCOPs) on gastroduodenal injury. Seventy-two specific pathogen-free (SPF) male Sprague Dawley (SD) rats were randomly divided into six groups according to body weight: normal control group, ethanol group, whey protein group (500 mg/kg BW), and three TCOPs dose groups (250, 500, 1000 mg/kg BW). After intragastric administration for 30 days, the acute gastroduodenal injury was induced by anhydrous ethanol (5 mL/kg, intragastrically) in all groups except the normal control group. Biomarkers in gastric and duodenal tissue and serum were measured. Furthermore, western blot was used to detect the expression of apoptosis-related proteins. The results showed that the administration with TCOPs significantly reduced gastric and duodenal ulcer index, increased gastric juice pH, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, along with the reduction of malondialdehyde (MDA) contents. TCOPs decreased tumor Necrosis Factor-α (TNF-α), interleukin-1ß (IL-1ß), and myeloperoxidase (MPO) levels, while interleukin- 10 (IL-10) levels were increased. Furthermore, pepsinogens 1 (PG1), pepsinogens 2 (PG2), gastrin (GAS), and the pepsinogen ratio (PGR) were decreased, the prostaglandin E2 (PGE2) and NO contents were increased after TCOPs intervention. Moreover, TCOPs up-regulated the expression of Bcl-2 and inhibited the expression of Bax and Caspase-3. In conclusion, TCOPs have protective effects on ethanol-induced gastroduodenal injury through gastrointestinal mucosal microcirculation promotion, antioxidation, anti-inflammation, and anti-apoptosis mechanisms.


Assuntos
Anti-Inflamatórios/farmacologia , Etanol/efeitos adversos , Oligopeptídeos/isolamento & purificação , Oligopeptídeos/farmacologia , Tilápia/metabolismo , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Biomarcadores , Catalase/metabolismo , Colágeno , Citocinas/metabolismo , Modelos Animais de Doenças , Trato Gastrointestinal/lesões , Interleucina-1beta , Masculino , Malondialdeído/metabolismo , Peroxidase/metabolismo , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
8.
Nutrients ; 13(6)2021 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-34205338

RESUMO

This study investigated the antioxidant effects of whey protein peptide on learning and memory in aging C57BL/6N mice. A total of 72 SPF male C57BL/6N mice were used. Twelve mice were randomly selected as the control group, and the other mice were intraperitoneally injected with D-galactose (100 mg/kg body weight for 6 weeks), during which, the mice in the control group were intraperitoneally injected with the same amount of normal saline. After 6 weeks, the blood was taken from the epicanthus and the serum MDA level was measured, according to which, the mice were randomly divided into the model control group, the whey protein group (1.5 g/kg body weight), and three Whey protein peptide (WHP) intervention groups (0.3 g/kg body weight, 1.5 g/kg body weight, 3.0 g/kg body weight). The water solution of the test sample was administered by oral gavage every day. The intervention period was 30 days, during which, the model control group, the whey protein group, and the whey protein peptide group continued receiving intraperitoneal injections of D-galactose, while the control group continued receiving intraperitoneal injections of normal saline. After the intervention, behavioral experiments were conducted in the following order: open field test, water maze test, and new object recognition test. After the behavioral experiment, the morphology of hippocampal formation was observed by HE staining and TUNEL labeling. Oxidative stress-related indexes in the serum, liver, and brain were detected. Expression levels of the cholinergic system-related enzymes and proinflammatory cytokines in brain tissue were detected. Western blot was used to detect the expression of synaptic plasticity-related proteins in the mouse brain. The results showed that WHP could significantly improve the accumulation of MDA and PC, increase the activities of SOD and GSH-Px, resist oxidative stress injury, and enhance the potential of endogenous antioxidant defense mechanisms. WHP can significantly improve the decline of aging-related spatial exploration, body movement, and spatial and non-spatial learning/memory ability. Its specific mechanism may be related to reducing the degeneration of hippocampal nerve cells, reducing the apoptosis of nerve cells, improving the activity of AChE, reducing the expression of inflammatory factors (TNF-α and IL-1ß) in brain tissue, reducing oxidative stress injury, and improving the expression of p-CaMKⅡ and BDNF synaptic plasticity protein. These results indicate that WHP can improve aging-related oxidative stress, as well as learning and memory impairment.


Assuntos
Envelhecimento/fisiologia , Antioxidantes/farmacologia , Aprendizagem/efeitos dos fármacos , Memória/efeitos dos fármacos , Peptídeos/administração & dosagem , Proteínas do Soro do Leite/química , Envelhecimento/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Galactose/administração & dosagem , Hipocampo/citologia , Marcação In Situ das Extremidades Cortadas , Masculino , Malondialdeído/sangue , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Estresse Oxidativo/efeitos dos fármacos
9.
Artigo em Inglês | MEDLINE | ID: mdl-34279752

RESUMO

OBJECTIVES: We sought to distinguish area at risk from salvage myocardial zone and to predict left ventricle functional recovery in the convalescent stage by Texture Analysis (TA) of T2-Mapping. METHODS: One hundred and six patients diagnosed with AMI and treated with percutaneous coronary intervention (PCI) underwent acute cardiac magnetic resonance imaging (CMR) and 45 of whom had a subsequent CMR scan following recovery. Cine imaging, T2-Mapping, T2-weighted STIR imaging, and LGE imaging were performed. In the texture analysis, regions of interest (infarcted, salvageable, and remote) were drawn by two blinded, independent readers. RESULTS: Seven independent texture features on T2-Mapping were selected: Perc.50%, S(2,2)InvDfMom, S(2.-2)AngScMom, S(4,0)Entropy, 45dgrLngREmph, 45dgr_Fraction and 135dr_GLevNonU. Among them, the average value of 135dr_GLevNonU in the infarct zone, AAR zone, and the remote zone was: 61.96±26.03, 31.811±18.933 and 99.839±26.231, respectively. Additionally, 135dr_GLevNonU provided the highest area under the curve (AUC) from the receiver operating characteristic curve (ROC curve) for distinguishing AAR from the infarct zone in each subgroup (all patients, patients with MVO and)were 0.845 ± 0.052 0.855 ± 0.083 and 0.845 ± 0.066, respectively, and were more promise than T2-Mapping mean (p<0.001). The AUC for differentiating AAR from the remote zone is 0.942±0.041. Texture features are not associated with convalescent decreased strain, ejection fraction (EF) or left ventricle remodeling (LVR) in analysis (p>0.05). CONCLUSION: TA of T2-mapping can distinguish AAR from both the infarct zone and the remote myocardial zone without LGE imaging in reperfused AMI. However, these features are not able to predict patients' functional recovery in the convalescent stage.

10.
Breast Cancer Res Treat ; 189(1): 103-110, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34120223

RESUMO

PURPOSE: Chemotherapy-related amenorrhea (CRA) is a surrogate for ovarian toxicity and associated risk of infertility and premature menopause. Here, we compare CRA rate with paclitaxel (T)-trastuzumab (H) to that with ado-trastuzumab emtansine (T-DM1). METHODS: Patients with T1N0 HER2 + early-stage breast cancer (eBC) enrolled on the ATEMPT trial and were randomized 3:1 to T-DM1 3.6 mg/kg IV every (q) 3 weeks (w) × 17 vs. T 80 mg/m2 with H IV qw × 12 (4 mg/kg load → 2 mg/kg), followed by H (6 mg/kg IV q3w × 13). Enrollees who self-reported as premenopausal were asked to complete menstrual surveys at baseline and every 6-12 months for 60 months. 18-month CRA (no periods reported during prior 6 months on 18-month survey) was the primary endpoint of this analysis. RESULTS: Of 512 ATEMPT enrollees, 123 who began protocol therapy and answered baseline and at least one follow-up menstrual survey were premenopausal at enrollment. 76 had menstrual data available at 18 months without having received a gonadotropin-releasing hormone agonist or undergone hysterectomy and/or oophorectomy. Median age was 45 (range 23-53) among 18 who had received TH and 46 (range 34-54) among 58 who had received T-DM1. The 18-month rate of CRA was 50% after TH and 24% after T-DM1 (p = 0.045). CONCLUSION: Amenorrhea at 18 months was less likely in recipients of adjuvant T-DM1 than TH. Future studies are needed to understand how T-DM1 impacts risk of infertility and permanent menopause, and to assess amenorrhea rates when T-DM1 is administered after standard HER2-directed chemotherapy regimens.


Assuntos
Neoplasias da Mama , Maitansina , Ado-Trastuzumab Emtansina/efeitos adversos , Adulto , Amenorreia/induzido quimicamente , Amenorreia/epidemiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Maitansina/efeitos adversos , Pessoa de Meia-Idade , Paclitaxel/efeitos adversos , Paclitaxel/uso terapêutico , Receptor ErbB-2/genética , Trastuzumab/efeitos adversos , Adulto Jovem
11.
J Clin Oncol ; 39(21): 2375-2385, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34077270

RESUMO

PURPOSE: The ATEMPT trial was designed to determine if treatment with trastuzumab emtansine (T-DM1) caused less toxicity than paclitaxel plus trastuzumab (TH) and yielded clinically acceptable invasive disease-free survival (iDFS) among patients with stage I human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC). METHODS: Patients with stage I centrally confirmed HER2+ BC were randomly assigned 3:1 to T-DM1 or TH and received T-DM1 3.6 mg/kg IV every 3 weeks for 17 cycles or T 80 mg/m2 IV with H once every week × 12 weeks (4 mg/kg load →2 mg/kg), followed by H × 39 weeks (6 mg/kg once every 3 weeks). The co-primary objectives were to compare the incidence of clinically relevant toxicities (CRTs) in patients treated with T-DM1 versus TH and to evaluate iDFS in patients receiving T-DM1. RESULTS: The analysis population includes all 497 patients who initiated protocol therapy (383 T-DM1 and 114 TH). CRTs were experienced by 46% of patients on T-DM1 and 47% of patients on TH (P = .83). The 3-year iDFS for T-DM1 was 97.8% (95% CI, 96.3 to 99.3), which rejected the null hypothesis (P < .0001). Serially collected patient-reported outcomes indicated that patients treated with T-DM1 had less neuropathy and alopecia and better work productivity compared with patients on TH. CONCLUSION: Among patients with stage I HER2+ BC, one year of adjuvant T-DM1 was associated with excellent 3-year iDFS, but was not associated with fewer CRT compared with TH.

12.
Cancer Imaging ; 21(1): 38, 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34039403

RESUMO

BACKGROUND: Early recurrence of oesophageal squamous cell carcinoma (SCC) is defined as recurrence after surgery within 1 year, and appears as local recurrence, distant recurrence, and lymph node positive and disseminated recurrence. Contrast-enhanced computed tomography (CECT) is recommended for diagnosis of primary tumor and initial staging of oesophageal SCC, but it cannot be used to predict early recurrence. It is reported that radiomics can help predict preoperative stages of oesophageal SCC, lymph node metastasis before operation, and 3-year overall survival of oesophageal SCC patients following chemoradiotherapy by extracting high-throughput quantitative features from CT images. This study aimed to develop models based on CT radiomics and clinical features of oesophageal SCC to predict early recurrence of locally advanced cancer. METHODS: We collected electronic medical records and image data of 197 patients with confirmed locally advanced oesophageal SCC. These patients were randomly allocated to 137 patients in the training cohort and 60 in the test cohort. 352 radiomics features were extracted by delineating region-of-interest (ROI) around the lesion on CECT images and clinical signature was generated by medical records. The radiomics model, clinical model, the combined model of radiomics and clinical features were developed by radiomics features and/or clinical characteristics. Predicting performance of the three models was assessed with area under receiver operating characteristic curve (AUC), accuracy and F-1 score. RESULTS: Eleven radiomics features and/or six clinical signatures were selected to build prediction models related to recurrence of locally advanced oesophageal SCC after trimodal therapy. The AUC of integration of radiomics and clinical models was better than that of radiomics or clinical model for the training cohort (0.821 versus 0.754 or 0.679, respectively) and for the validation cohort (0.809 versus 0.646 or 0.658, respectively). Integrated model of radiomics and clinical features showed good performance in predicting early recurrence of locally advanced oesophageal SCC for both the training and validation cohorts (accuracy = 0.730 and 0.733, and F-1score = 0.730 and 0.778, respectively). CONCLUSIONS: The integrated model of CECT radiomics and clinical features may be a potential imaging biomarker to predict early recurrence of locally advanced oesophageal SCC after trimodal therapy.


Assuntos
Meios de Contraste/uso terapêutico , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/radioterapia , Radiometria/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
13.
Ann Surg Oncol ; 28(11): 6071-6082, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33881656

RESUMO

BACKGROUND: The impact of patient demographics and local therapy choice on arm morbidity in young breast cancer patients is understudied despite its importance given the long survivorship period. This study assessed patient-reported arm morbidity in the Young Women's Breast Cancer Study (YWS), a prospective cohort study. METHODS: From 2006 to 2016, 1302 women with breast cancer diagnosed at the age of 40 years or younger enrolled in the YWS. The participants regularly complete surveys. The response rates are higher than 86%. Using the Breast Cancer Prevention Trial Checklist, this study examined the prevalence of patient-reported postoperative arm swelling and decreased range of motion (ROM) 1 year after diagnosis, stratified by local therapy strategy, in patients who had surgery for stages 1 to 3 disease. Logistic regression analysis was used to identify risk factors for arm morbidity. RESULTS: Among 888 eligible participants (median age, 37 years), 14% reported arm swelling and 34% reported decreased ROM at 1 year. Arm swelling was reported by 23.6% of the patients who had axillary lymph node dissection (ALND) and 24.6% of the patients who received ALND and post-mastectomy radiation therapy (PMRT). In the multivariable analysis, the patients who reported being financially uncomfortable or who had ALND were at higher risk of arm swelling at 1 year. Being overweight, receiving ALND after sentinel lymph node biopsy, and receiving PMRT were associated with decreased ROM at 1 year. CONCLUSION: High rates of self-reported arm morbidity in young breast cancer survivors were reported, particularly in patients receiving ALND and PMRT. Attention to the risks and benefits of differing local therapy strategies for ALND and PMRT patients is warranted.


Assuntos
Neoplasias da Mama , Adulto , Braço , Axila , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Excisão de Linfonodo/efeitos adversos , Metástase Linfática , Mastectomia , Morbidade , Estudos Prospectivos , Biópsia de Linfonodo Sentinela
14.
Nutrients ; 13(3)2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33801268

RESUMO

Radiation therapy is widely used in the treatment of tumor diseases, but it can also cause serious damage to the body, so it is necessary to find effective nutritional supplements. The main purpose of this study is to evaluate the protective effect of whey hydrolysate peptides (WHPs) against 60Coγ radiation damage in mice and explore the mechanism. BALB/c mice were given WHPs by oral gavage administration for 14 days. Then, some mice underwent a 30-day survival test after 8 Gy radiation, and other mice received 3.5 Gy radiation to analyze the changes in body weight, hematology and bone marrow DNA after three and 14 days. In addition, through further analysis of the level of oxidative stress and intestinal barrier function, the possible mechanism of the radioprotective effect of WHPs was explored. The study found WHPs can prolong survival time, restore body weight, and increase the number of peripheral blood white blood cells and bone marrow DNA content in irradiated mice. In addition, WHPs can significantly improve the antioxidant capacity, inhibit pro-inflammatory cytokines and protect the intestinal barrier. These results indicate that WHPs have a certain radioprotective effect in mice, and the main mechanism is related to reducing oxidative damage.


Assuntos
Raios gama/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Protetores contra Radiação/farmacologia , Soro do Leite , Animais , Antioxidantes/farmacologia , Peso Corporal , Medula Óssea/efeitos dos fármacos , Medula Óssea/efeitos da radiação , Citocinas , Dano ao DNA , Modelos Animais de Doenças , Feminino , Intestinos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Radioterapia/efeitos adversos
15.
Cancer Immunol Immunother ; 70(10): 2991-3000, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33745032

RESUMO

BACKGROUND: Checkpoint kinase 1 (CHK1) has dual roles in both the DNA damage response and in the innate immune response to genotoxic stress. The combination of CHK1 inhibition and immune checkpoint blockade has the potential to enhance anti-tumoral T-cell activation. METHODS: This was an open-label phase 1 study evaluating the CHK1 inhibitor prexasertib and the anti-PD-L1 antibody LY3300054. After a lead-in of LY3300054 (Arm A), prexasertib (Arm B) or the combination (Arm C), both agents were administered intravenously at their respective recommended phase 2 doses (RP2Ds) on days 1 and 15 of a 28-day cycle. Flow cytometry of peripheral blood was performed before and during treatment to analyze effects on immune cell populations, with a focus on T cell subsets and activation. Plasma cytokines and chemokines were analyzed using the Luminex platform. RESULTS: Among seventeen patients enrolled, the combination was tolerable at the monotherapy RP2Ds, 105 mg/m2 prexasertib and 700 mg LY3300054. Dose-limiting toxicities included one episode each of febrile neutropenia (Arm C) and grade 4 neutropenia lasting > 5 days (Arm B). One patient had immune-related AST/ALT elevation after 12 cycles. Three patients with CCNE1-amplified, high-grade serous ovarian cancer (HGSOC) achieved partial response (PR), 2 lasting > 12 months; a fourth such patient maintained stable disease > 12 months. Analysis of peripheral blood demonstrated evidence of CD8 + T-cell activation in response to treatment. CONCLUSIONS: Prexasertib in combination with PD-L1 blockade was tolerable and demonstrated preliminary activity in CCNE1-amplified HGSOC with evidence of cytotoxic T-cell activation in patient blood samples. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03495323. Registered April 12, 2018.


Assuntos
Antineoplásicos/uso terapêutico , Cistadenocarcinoma Seroso/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Pirazinas/uso terapêutico , Pirazóis/uso terapêutico , Adulto , Idoso , Antineoplásicos/farmacologia , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Pirazinas/farmacologia , Pirazóis/farmacologia
16.
Eur Heart J Cardiovasc Imaging ; 22(8): 844-851, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-33686389

RESUMO

AIMS: In order to determine acute cardiac involvement in patients with COVID-19, we quantitatively evaluated tissue characteristics and mechanics by non-invasive cardiac magnetic resonance (CMR) in a cohort of patients within the first 10 days of the onset of COVID symptoms. METHODS AND RESULTS: Twenty-five patients with reverse transcription polymerase chain reaction confirmed COVID-19 and at least one marker of cardiac involvement [cardiac symptoms, abnormal electrocardiograph (ECG), or abnormal cardiac biomarkers] and 25 healthy age- and gender-matched control subjects were recruited to the study. Patients were divided into those with elevated (n = 8) or normal TnI (n = 17). There were significant differences in global longitudinal strain among patients who were positive and negative for hs-TnI, and controls [-12.3 (-13.3, -11.5)%, -13.1 (-14.2, -9.8)%, and -15.7 (-18.3, -12.7)%, P = 0.004]. Native myocardial T1 relaxation times in patients with positive and negative hs-TnI manifestation (1169.8 ± 12.9 and 1113.2 ± 31.2 ms) were significantly higher than the normal (1065 ± 57 ms) subjects, respectively (P < 0.001). The extracellular volume (ECV) of patients who were positive and negative for hs-TnI was higher than that of the normal controls [32 (31, 33)%, 29 (27, 30)%, and 26 (24, 27.5)%, P < 0.001]. In our study, quantitative T2 mapping in patients who were positive and negative for hs-TnI [51 (47.9, 52.8) and 48 (47, 49.4) ms] was significantly higher than the normal [42 (41, 45.2) ms] subjects (P < 0.001). CONCLUSION: In patients with early-stage COVID-19, myocardial oedema, and functional abnormalities are a frequent finding, while irreversible regional injury such as necrosis may be infrequent.


Assuntos
COVID-19 , Estudos de Casos e Controles , Humanos , Imageamento por Ressonância Magnética , Imagem Cinética por Ressonância Magnética , Miocárdio , Valor Preditivo dos Testes , Estudos Prospectivos , SARS-CoV-2
17.
J Magn Reson Imaging ; 54(1): 290-300, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33604934

RESUMO

BACKGROUND: Noncontrast cardiac T1 times are increased in dialysis patients which might indicate fibrotic alterations in uremic cardiomyopathy. PURPOSE: To explore the application of the texture analysis (TA) of T1 images in the assessment of myocardial alterations in dialysis patients. STUDY TYPE: Case-control study. POPULATION: A total of 117 subjects, including 22 on hemodialysis, 44 on peritoneal dialysis, and 51 healthy controls. FIELD STRENGTH: A 3 T, steady-state free precession (SSFP) sequence, modified Look-Locker imaging (MOLLI). ASSESSMENT: Two independent, blinded researchers manually delineated endocardial and epicardial borders of the left ventricle (LV) on midventricular T1 maps for TA. STATISTICAL TESTS: Texture feature selection was performed, incorporating reproducibility verification, machine learning, and collinearity analysis. Multivariate linear regressions were performed to examine the independent associations between the selected texture features and left ventricular function in dialysis patients. Texture features' performance in discrimination was evaluated by sensitivity and specificity. Reproducibility was estimated by the intraclass correlation coefficient (ICC). RESULTS: Dialysis patients had greater T1 values than normal (P < 0.05). Five texture features were filtered out through feature selection, and four showed a statistically significant difference between dialysis patients and healthy controls. Among the four features, vertical run-length nonuniformity (VRLN) had the most remarkable difference among the control and dialysis groups (144 ± 40 vs. 257 ± 74, P < 0.05), which overlap was much smaller than Global T1 times (1268 ± 38 vs. 1308 ± 46 msec, P < 0.05). The VRLN values were notably elevated (cutoff = 170) in dialysis patients, with a specificity of 97% and a sensitivity of 88%, compared with T1 times (specificity = 76%, sensitivity = 60%). In dialysis patients, VRLN was significantly and independently associated with left ventricular ejection fraction (P < 0.05), global longitudinal strain (P < 0.05), radial strain (P < 0.05), and circumferential strain (P < 0.05); however, T1 was not. DATA CONCLUSION: The texture features obtained by TA of T1 images and VRLN may be a better parameter for assessing myocardial alterations than T1 times. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 3.


Assuntos
Cardiomiopatias , Função Ventricular Esquerda , Cardiomiopatias/diagnóstico por imagem , Estudos de Casos e Controles , Humanos , Imageamento por Ressonância Magnética , Imagem Cinética por Ressonância Magnética , Miocárdio , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Volume Sistólico
18.
Biochem Pharmacol ; 186: 114475, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33609560

RESUMO

Autophagy has become a promising target for cancer therapy. Fangchinoline (Fan) has been shown to exert anticancer effects in some types of cancers. However, the anticancer effects on colorectal cancer (CRC) and the underlying mechanisms have never been elucidated. More specifically, regulation of autophagy in CRC by Fan has never been reported before. In the present study, Fan was found to induce apoptosis and autophagic flux in the CRC cell lines HT29 and HCT116, which was reflected by the enhanced levels of LC3-II protein and p62 degradation, and the increased formation of autophagosomes and puncta formation by LC3-II. Meanwhile, combination with the early-stage autophagy inhibitor 3-methyladenine (3-MA) but not the late-stage autophagy inhibitor chloroquine (CQ) further increased Fan-induced cell death, which suggested the cytoprotective function of autophagy induced by Fan in both HT29 and HCT116 cells. Moreover, Fan treatment demonstrated a dose- and time-dependently increase in the phosphorylation of AMPK and decrease in the phosphorylation of mammalian target of rapamycin (mTOR) and ULK1, leading to the activation of the AMPK/mTOR/ULK1 signaling pathway. Furthermore, in the HT29 xenograft model, Fan inhibited tumor growth in vivo. These results indicate that Fan inhibited CRC cell growth both in vitro and in vivo and revealed a new molecular mechanism involved in the anticancer effect of Fan on CRC, suggesting that Fan is a potent autophagy inducer and might be a promising anticancer agent.


Assuntos
Antineoplásicos/uso terapêutico , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Benzilisoquinolinas/uso terapêutico , Neoplasias Colorretais/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Quinases/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Antineoplásicos/farmacologia , Autofagia/efeitos dos fármacos , Autofagia/fisiologia , Benzilisoquinolinas/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Células HCT116 , Células HT29 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
19.
IEEE Trans Image Process ; 30: 2587-2598, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33417553

RESUMO

Deep face recognition has achieved great success due to large-scale training databases and rapidly developing loss functions. The existing algorithms devote to realizing an ideal idea: minimizing the intra-class distance and maximizing the inter-class distance. However, they may neglect that there are also low quality training images which should not be optimized in this strict way. Considering the imperfection of training databases, we propose that intra-class and inter-class objectives can be optimized in a moderate way to mitigate overfitting problem, and further propose a novel loss function, named sigmoid-constrained hypersphere loss (SFace). Specifically, SFace imposes intra-class and inter-class constraints on a hypersphere manifold, which are controlled by two sigmoid gradient re-scale functions respectively. The sigmoid curves precisely re-scale the intra-class and inter-class gradients so that training samples can be optimized to some degree. Therefore, SFace can make a better balance between decreasing the intra-class distances for clean examples and preventing overfitting to the label noise, and contributes more robust deep face recognition models. Extensive experiments of models trained on CASIA-WebFace, VGGFace2, and MS-Celeb-1M databases, and evaluated on several face recognition benchmarks, such as LFW, MegaFace and IJB-C databases, have demonstrated the superiority of SFace.

20.
J Magn Reson Imaging ; 53(2): 516-526, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32841481

RESUMO

BACKGROUND: Acute myocardial infarction (AMI) is a disease with high morbidity and mortality worldwide and the evaluation of myocardial injury and perfusion status following myocardial ischemia and reperfusion is of clinical value. PURPOSE: To assess the diagnostic utility of simplified perfusion fraction (SPF) in differentiating salvage and infarcted myocardium and its predictive value for left ventricular remodeling in patients with reperfusion ST-segment elevation myocardial infarction (STEMI). STUDY TYPE: Prospective. POPULATION: Forty-one reperfused STEMI patients and 20 healthy volunteers. FIELD STRENGTH/SEQUENCE: 3.0T MRI. The MR examination included cine, T2 -short tau inversion recovery (T2 -STIR), first pass perfusiong (FPP),phase sensitive inversion recovery (PSIR), and diffusion-weighted imaging (DWI). ASSESSMENT: SPF values among different myocardium regions (infarcted, salvaged, remote, and MVO) and stages of reperfused STEMI patients as well as normal controls were measured. The diagnostic utility of SPF values in differentiating salvaged and infarcted myocardium was assessed. STATISTICAL ANALYSIS: Independent t-test and the Mann-Whitney U-test. Logistic regression. RESULTS: SPF values in healthy controls were not significantly different than SPF values in the remote myocardium of patients (40.09 ± 1.47% vs. 40.28 ± 1.93%, P = 0.698). In reperfusion STEMI patients, SPF values were lower in infarcted myocardium compared to remote and salvaged myocardium (32.15 ± 2.36% vs. 40.28 ± 1.93%, P < 0.001; 32.15 ± 2.36% vs. 36.68 ± 2.71%, P < 0.001). SPF values of infarcted myocardium showed a rebound increase from acute to convalescent stages (32.15 ± 2.36% vs. 34.69 ± 3.69%, P < 0.001). When differentiating infarcted and salvaged myocardium, SPF values demonstrated an area under the curve (AUC) of 0.89 (sensitivity 85.4%, specificity 80.5%, cutoff 34.42%). Lower SPF values were associated with lower odds ratio (OR = 0.304) of left ventricular remodeling after adjusting for potential confounders with a confidence interval (CI) of 0.129-0.717, P = 0.007. DATA CONCLUSION: SPF might be able to differentiate salvaged and infarcted myocardium and is a strong predictor of left ventricular remodeling in reperfused STEMI patients. Level of Evidence 2 Technical Efficacy Stage 2.


Assuntos
Infarto do Miocárdio , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Imagem Cinética por Ressonância Magnética , Infarto do Miocárdio/diagnóstico por imagem , Miocárdio , Perfusão , Valor Preditivo dos Testes , Estudos Prospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Função Ventricular Esquerda
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