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BACKGROUND: The antiviral drug Nirmatrelvir was found to be a key drug in controlling the progression of pneumonia during the infectious phase of COVID-19. However, there are very few options for effective treatment for cancer patients who have viral pneumonia. Glucocorticoids is one of the effective means to control pneumonia, but there are many adverse events. EGCG is a natural low toxic compound with anti-inflammatory function. Thus, this study was designed to investigate the safety and efficacy of epigallocatechin-3-gallate (EGCG) aerosol to control COVID-19 pneumonia in cancer populations. METHODS: The study was designed as a prospective, single-arm, open-label phase I/II trial at Shandong Cancer Hospital and Institute, between January 5, 2023 to March 31,2023 with viral pneumonia on radiographic signs after confirmed novel coronavirus infection. These patients were treated with EGCG nebulization 10 ml three times daily for at least seven days. EGCG concentrations were increased from 1760-8817umol/L to 4 levels with dose escalation following a standard Phase I design of 3-6 patients per level. Any grade adverse event caused by EGCG was considered a dose-limiting toxicity (DLT). The maximum tolerated dose (MTD) is defined as the highest dose with less than one-third of patients experiencing dose limiting toxicity (DLT) due to EGCG. The primary end points were the toxicity of EGCG and CT findings, and the former was graded by Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0. The secondary end point was the laboratory parameters before and after treatment. RESULT: A total of 60 patients with high risk factors for severe COVID-19 pneumonia (factors such as old age, smoking and combined complications)were included in this phase I-II study. The 54 patients in the final analysis were pathologically confirmed to have tumor burden and completed the whole course of treatment. A patient with bucking at a level of 1760 umol/L and no acute toxicity associated with EGCG has been reported at the second or third dose gradients. At dose escalation to 8817umol/L, Grade 1 adverse events of nausea and stomach discomfort occurred in two patients, which resolved spontaneously within 1 hour. After one week of treatment, CT showed that the incidence of non-progression of pneumonia was 82% (32/39), and the improvement rate of pneumonia was 56.4% (22/39). There was no significant difference in inflammation-related laboratory parameters (white blood cell count, lymphocyte count, IL-6, ferritin, C-reactive protein and lactate dehydrogenase) before and after treatment. CONCLUSION: Aerosol inhalation of EGCG is well tolerated, and preliminary investigation in cancer population suggests that EGCG may be effective in COVID-19-induced pneumonia, which can promote the improvement of patients with moderate pneumonia or prevent them from developing into severe pneumonia. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05758571. Date of registration: 8 February 2023.
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COVID-19 , Catequina , Neoplasias , Pneumonia Viral , Humanos , Catequina/efeitos adversos , Catequina/análogos & derivados , Catequina/uso terapêutico , Oxigênio , Pneumonia Viral/epidemiologia , Estudos Prospectivos , Aerossóis e Gotículas Respiratórios , Resultado do TratamentoRESUMO
Radiation-induced oral mucositis has a dismal outcome with limited treatment options. We conducted a phase I study to evaluate the safety and preliminary efficacy of epigallocatechin-3-gallate (EGCG) mouthwash when given along with radiation in head and neck cancer. Patients with pathologically confirmed head and neck cancer were eligible for this study. EGCG mouthwash was administered at the assigned dosage level (starting at 440 µmol/L, three times a day) in a standard 3 + 3 dose escalation design. Mucosal toxicity, patient satisfaction, and mucositis-related pain (MTP) were assessed weekly. The primary endpoint was safety of EGCG, and the secondary endpoint was to determine the relief of the mucositis symptom. The pre- and post-treatment parameters were compared using the paired t-test. 20 patients were enrolled. The maximum tolerated dose of the EGCG mouthwash was 2200 µmol/L. Burning (n = 1/20) and nausea (n = 3/20) were the most common toxicities. No patients experienced WHO Grade 3 or higher mucositis. MTP scores significantly decreased after EGCG administration over time (p < 0.05). Adding EGCG mouthwash to radiotherapy is feasible without increasing toxicities. The recommended dose for phase II study is determined to be 1760 µmol/L, and EGCG administration reduces radiation-induced oral mucosal injury in patients.
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Catequina/análogos & derivados , Quimiorradioterapia , Neoplasias de Cabeça e Pescoço/terapia , Antissépticos Bucais/administração & dosagem , Mucosite/tratamento farmacológico , Lesões por Radiação/tratamento farmacológico , Adulto , Idoso , Catequina/administração & dosagem , Catequina/efeitos adversos , Humanos , Dose Máxima Tolerável , Pessoa de Meia-Idade , Mucosa Bucal/efeitos dos fármacos , Antissépticos Bucais/efeitos adversos , Mucosite/etiologia , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: To assess the spatial epidemic characteristics of TB and identify the key areas for disease prevention and control. OBJECTIVE: To explore the spatial distribution and socioeconomic influencing factors of TB in mainland China from 2013 to 2016. METHODS: Spatial autocorrelation was used to explore the spatial distribution characteristics of TB at the quantitative level. Ordinary least squares (OLS) and geographically weighted regression (GWR) models were conducted to explore the association between factors and TB incidence from both global and local perspectives. RESULTS: There was a significant positive spatial autocorrelation of TB at the provincial level (P < 0.05): hot spots were mainly located in the west of Xinjiang and Tibet, and cold spots in the eastern coastal areas. Four latent factors on the socioeconomic dimension, involving the proportion of illiterate people aged 15 and over, per capita disposable income in rural areas, the number of health technicians per 1000 population and the urban population density, were associated with TB incidence. The GWR model showed that the effect of the same factor on TB incidence varied with geographical location. CONCLUSIONS: Spatial clustering of TB incidence in mainland China still exists. The differences of socioeconomic factors in different locations can be confirmed by GWR model. Targeted preventive and control measures or policies will be conducive in effectively reducing the incidence of TB, especially in hot spots.
CONTEXTE: Evaluer les caractéristiques spatiales épidémiques de la tuberculose (TB) et identifier les domaines clés pour la prévention et le contrôle de la maladie. OBJECTIF: Explorer la distribution spatiale et les facteurs d'influence socioéconomiques de la TB en Chine continentale de 2013 à 2016. MÉTHODES: Une autocorrélation spatiale a été utilisée pour explorer les caractéristiques de distribution spatiale de la TB à une échelle quantitative. Les moindres carrés ordinaires (OLS) et des modèles de régression géographiquement pondérés (GWR) ont été utilisés pour explorer l'association entre les facteurs et l'incidence de la TB, tant du point de vue global que local. RÉSULTATS: Il y avait une autocorrélation spatiale positive significative au niveau provincial (P <0,05): les points chauds étaient principalement situés à l'ouest du Xinjiang et du Tibet et les points froids dans les zones côtières est. Quatre facteurs latents de dimension socioéconomique, à savoir la proportion d'analphabètes âgés de 15 ans et plus, le revenu disponible par habitant en zone rurale, le nombre de techniciens de la santé pour 1000 habitants et la densité de la population urbaine ont été associés à l'incidence de la TB. Le modèle GWR a montré que l'effet du même facteur sur l'incidence de la TB variait avec la localisation géographique. CONCLUSIONS: Le regroupement spatial de l'incidence de la TB en Chine continentale existe toujours. Les différences de facteurs socioéconomiques dans différents endroits peuvent être confirmées par le modèle GWR. Des mesures ou politiques de prévention et de contrôle ciblées permettront de réduire efficacement l'incidence de la TB, en particulier dans les zones les plus touchées.
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Mapeamento Geográfico , Fatores Socioeconômicos , Tuberculose/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Características de Residência , Análise Espacial , Adulto JovemRESUMO
Background: Radiation skin injury (RSI) causes changes in skin temperature, but detailed information on the thermographic responses is currently lacking. We investigated thermographic patterns after radiotherapy. We hypothesized that skin temperature may be used as a diagnostic and early predictor of RSI severity.Method: All breast cancer patients received radiotherapy after unilateral postmastectomy. The contralateral supraclavicular area served as control, and the frontal thermal image of torso was taken by a thermal infrared imager weekly. We defined areas of interest on bilateral symmetrical supraclavicular area, and analyzed the difference of average and maximum skin temperature (DSTaverage and DSTmax) between them. The extent of the weekly variation in DST (DSTW) was calculated using a mathematical formula to represent a trend of skin temperature change. RSI and symptoms related to RSI were scored from baseline to 2 weeks after the end of radiotherapy.Results: Forty-one patients were enrolled in this study. In comparison to the baseline, the DSTaverage and DSTmax increased significantly over time during radiotherapy (p < .05). The onset of DST increase was accompanied by the onset of radiation dermatitis, and the maximal DST also appeared at the peak of Radiation Therapy Oncology Group (RTOG) and symptom scores. Radiation dose, DSTaverage, burning-feeling and pulling were the independent variables affecting RTOG score according to multivariate analysis (p < .001, p < .034, p < .001, p < .001). Patients with DSTWaverage >1.223 or DSTWmax >1.114 in second week showed a late higher dermatitis score (RTOG score ≥2).Conclusion: This study confirmed that RSI was associated with thermographic response. Our results suggested that the follow-up observations of skin temperature during radiotherapy could provide the objective evaluation criteria and prediction methods for RSI.
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Neoplasias da Mama/complicações , Neoplasias da Mama/radioterapia , Radiodermite/etiologia , Temperatura Cutânea/efeitos da radiação , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radiodermite/patologiaRESUMO
Understanding etiological role and epidemiological profile is needed to improve clinical management and prevention of acute respiratory infections (ARIs). A 5-year prospective study about active surveillance for outpatients and inpatients with ARIs was conducted in Gansu province, China, from January 2011 to November 2015. Respiratory specimens were collected from patients and tested for eight respiratory viruses using polymerase chain reaction (PCR) or reverse transcription polymerase chain reaction (RT-PCR). In this study, 2768 eligible patients with median age of 43 years were enrolled including pneumonia (1368, 49.2%), bronchitis (435, 15.7%), upper respiratory tract infection or URTI (250, 9.0%), and unclassified ARI (715, 25.8%). Overall, 29.2% (808/2768) were positive for any one of eight viruses, of whom 130 cases were identified with two or more viruses. Human rhinovirus (HRV) showed the highest detection rate (8.6%), followed by influenza virus (Flu, 7.3%), respiratory syncytial virus (RSV, 6.1%), human coronavirus (hCoV, 4.3%), human parainfluenza (PIV, 4.0%), adenovirus (ADV, 2.1%), human metapneumovirus (hMPV, 1.6%), and human bocavirus (hBoV, 0.7%). Compared with URTI, RSV was more likely identified in pneumonia (χ2 = 12.720, P < 0.001) and hCoV was more commonly associated with bronchitis than pneumonia (χ2 = 15.019, P < 0.001). In patients aged less than 5 years, RSV showed the highest detection rate and hCoV was the most frequent virus detected in adults and elderly. The clear epidemical seasons were observed in HRV, Flu, and hCoV infections. These findings could serve as a reference for local health authorities in drawing up further plans to prevent and control ARIs associated with viral etiologies.
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Hospitalização , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Viroses/epidemiologia , Viroses/virologia , Vírus/classificação , Vírus/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China/epidemiologia , Feminino , Hospitais , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Estudos Prospectivos , Infecções Respiratórias/patologia , Estações do Ano , Vírus/genética , Adulto JovemRESUMO
PURPOSE: To investigate whether the apparent diffusion coefficient (ADC) values acquired from diffusion-weighted magnetic resonance imaging (DW-MRI) are correlated with molecular markers Ki-67, hypoxia-inducible factor 1α (HIF-1α), and vascular endothelial growth factor (VEGF) in rectal cancer (RC). MATERIALS AND METHODS: Ninety-one patients (64 males and 27 females) diagnosed with rectal cancer underwent 3.0T DW-MRI before any anticancer treatment. DW-MRI was performed using the single-shot echo-planar imaging technique (b = 0 and b = 800 s/mm(2) ). The patients underwent surgery within 1 week after MRI. Ki-67, HIF-1α, and VEGF expression were assessed by immunohistochemistry at both the resected margins and the center of the tumor. RESULTS: We noted that ADC values correlated positively with histology differentiations (r = 0.336, P = 0.001) and negatively with carcinoembryonic antigen level (r = -0.217, P = 0.039) in RC. Both the value and the level of Ki-67 expression were correlated inversely with the ADC values (r = -0.475, P < 0.001 and r = -0.555, P < 0.001). There was a weak negative correlation between HIF-1α expression and the ADC values (r = -0.304, P = 0.003). VEGF expression was correlated inversely with the ADC values of the RCs (r = -0.290, P = 0.005). However, no significant correlation was observed between VEGF expression and the ADC values in pT4 RCs (r = -0.166, P = 0.255). CONCLUSION: Our results suggest that the ADC values on DW-MRI may be used as a measurement of cell proliferation and hypoxia in RC. J. Magn. Reson. Imaging 2016;44:594-600.
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Biomarcadores Tumorais/metabolismo , Imagem de Difusão por Ressonância Magnética/métodos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Antígeno Ki-67/metabolismo , Neoplasias Retais/metabolismo , Neoplasias Retais/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Retais/diagnóstico por imagem , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estatística como Assunto , Hipóxia TumoralRESUMO
BACKGROUND: Genes that regulate stem cell function are suspected to exert adverse effects on prognosis in malignancy. However, diverse cancer stem cell signatures are difficult for physicians to interpret and apply clinically. To connect the transcriptome and stem cell biology, with potential clinical applications, we propose a novel computational "gene-to-function, snapshot-to-dynamics, and biology-to-clinic" framework to uncover core functional gene-sets signatures. This framework incorporates three function-centric gene-set analysis strategies: a meta-analysis of both microarray and RNA-seq data, novel dynamic network mechanism (DNM) identification, and a personalized prognostic indicator analysis. This work uses complex disease acute myeloid leukemia (AML) as a research platform. RESULTS: We introduced an adjustable "soft threshold" to a functional gene-set algorithm and found that two different analysis methods identified distinct gene-set signatures from the same samples. We identified a 30-gene cluster that characterizes leukemic stem cell (LSC)-depleted cells and a 25-gene cluster that characterizes LSC-enriched cells in parallel; both mark favorable-prognosis in AML. Genes within each signature significantly share common biological processes and/or molecular functions (empirical p = 6e-5 and 0.03 respectively). The 25-gene signature reflects the abnormal development of stem cells in AML, such as AURKA over-expression. We subsequently determined that the clinical relevance of both signatures is independent of known clinical risk classifications in 214 patients with cytogenetically normal AML. We successfully validated the prognosis of both signatures in two independent cohorts of 91 and 242 patients respectively (log-rank p < 0.0015 and 0.05; empirical p < 0.015 and 0.08). CONCLUSION: The proposed algorithms and computational framework will harness systems biology research because they efficiently translate gene-sets (rather than single genes) into biological discoveries about AML and other complex diseases.
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Redes Reguladoras de Genes , Células-Tronco Hematopoéticas/metabolismo , Leucemia Mieloide Aguda/genética , Células-Tronco Neoplásicas/metabolismo , Transcriptoma , Algoritmos , Perfilação da Expressão Gênica , Humanos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/mortalidade , PrognósticoRESUMO
Stimuli-responsive theranostic agents represent a class of molecules that integrate therapeutic and diagnostic functions, offering the capability to respond to disease-associated biomarkers. Dual-stimuli responsive agents, particularly those based on small molecules, have shown considerable promise for precise imaging-guided therapeutic applications. In this Highlight, we summarize the progress of dual-stimuli responsive theranostic agents based on small molecules, for diagnostic and therapeutic studies in biological systems. The Highlight focuses on comparing different responsive groups and chemical structures of these dual-stimuli responsive theranostic agents towards different biomarkers. The potential future directions of the agents for further applications in biological systems are also discussed.
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BACKGROUND: Maintenance therapy (MT) for recurrent or metastatic cervical cancer remains non-standardized. This study assessed MT effectiveness using a comprehensive approach and identifies prognosis factors inpatients with recurrent or metastatic cervical cancer. METHODS: From January 2019 and December 2021, over 6000 patients from six Chinese institutions were retrospectively examined. Patients had recurrent/metastatic cervical cancer and underwent first-line chemotherapy with or without MT. We calculated overall and progression-free survival using Kaplan-Meier analysis, comparing via log-rank test, and conducted Cox regression for prognostic factors. RESULTS: Overall, 274 patients were stratified into an MT group (n = 77) and a non-MT group (n = 197). The 3-year OS rates were 52.5 % and 28.0 % for the MT and non-MT groups, respectively. The MT group had significantly enhanced median OS (37 vs. 21 months; HR, 0.43; 95 % CI, 0.30-0.61; P < 0.001) and PFS (21 vs. 14 months; HR, 0.65; 95 % CI, 0.47-0.90; P = 0.014) compared with the non-MT group. No significant differences in efficacy were observed among the various MT regimens, whether PD-1 monoclonal antibody, targeted therapeutic agents, or a combination of both. Extended PFS and OS were observed in patients receiving > 8 MT cycles. Multivariate analyses revealed that oligometastasis, MT, exclusive prior surgery (as opposed to combined surgery and radiotherapy), and extended interval before recurrence were independent OS predictors (P = 0.045, P < 0.001, P = 0.010, and P = 0.005, respectively); oligometastasis, concurrent radiotherapy, MT, and extended interval before recurrence were independent PFS predictors (P = 0.004, P = 0.007, P = 0.009, and P = 0.003). CONCLUSIONS: The MT integration markedly extended PFS and OS in patients diagnosed with recurrent or metastatic cervical cancer.
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Neoplasias do Colo do Útero , Feminino , Humanos , Prognóstico , Estudos Retrospectivos , Neoplasias do Colo do Útero/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Intervalo Livre de ProgressãoRESUMO
BACKGROUND: Colon cancer with liver metastases (CCLM) characterized by genetic heterogeneity is an evolutionary process leading to variations in response to selective pressure, but the underlying evolutionary models still remains unclear. METHODS: Total of 30 samples, including primary tumor and two to four matched liver metastases from 8 treatment-naïve patients with CCLM were collected, and subjected to whole-exome DNA sequencing. PyClone was used to calculate intra and inter-tumor heterogeneity, LICHeE was used to reconstruct the cancer phylogeny trees and investigate the subclonal composition. RESULTS: The genetic differences were observed between primary and metastatic lesions, as well as among multiple metastases in all patients. The natural history models of colorectal cancer in each case were identified, including parallel, linear, and branching evolution. Liver metastases could originate from primary lesions or other metastases. Pathway and process enrichment analysis also showed obvious heterogeneity and enhancement of several molecular functions. CONCLUSIONS: Our data reveal the genetic and heterogeneity between primary and metastatic lesions, as well as among multiple metastases and provide genomic evidence for clonal heterogeneity for CCLM.
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Neoplasias do Colo , Neoplasias Hepáticas , Humanos , Neoplasias do Colo/genética , Neoplasias Hepáticas/patologia , Genômica , MutaçãoRESUMO
To evaluate the safety and effectiveness of epigallocatechin-3-gallate (EGCG) solution treating the acute severe dermatitis in patients receiving radiotherapy. This phase I research enrolled patients with thoracic cancer receiving radiotherapy at Shandong Cancer Hospital and Institute in Shandong, China. EGCG solution was sprayed to the radiation field when grade III radiation-induced dermatitis (RID) first appearance. EGCG concentration escalated from 660 to 2574 µmol/L using modified-Fibonacci dose-escalation. RID and related symptoms were followed up every day. Between March 2021 and November 2021, 19 patients were enrolled in this phase I research. The median dose of grade III RID first observation was 44 Gy (30.6-52 Gy). As the EGCG treatment was performed continuously, all these grade III RID reactions were significantly decreased to grade I or grade II RID at three days after use of EGCG (p < 0.001). Significant relief can be observed in burning sensation (p < 0.001), tractive sensation (p < 0.001), tenderness (p < 0.001), erythema (p < 0.001), itching (p < 0.001) and pain (p < 0.001) after 15 days of EGCG treatment. No radiation therapy delay or interruption for all 19 patients. No adverse events were observed and reported associated with EGCG. The highest dose of this Phase I trial (2574 µmol/L) was recommended for continuous Phase II trial for further evaluation. In this phase I clinical research, use of EGCG solution is safe and can significantly relief grade III RID in patients receiving radiotherapy. Thus, EGCG might be a new choice for acute sever RID.Trial Registration: ClinicalTrials.gov Identifier: NCT02580279 (Full date of first registration: 12/2014).
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Catequina , Dermatite , Neoplasias , Radiodermite , Humanos , Neoplasias/complicações , Neoplasias/radioterapia , Catequina/efeitos adversos , Radiodermite/tratamento farmacológico , Radiodermite/etiologia , Doença AgudaRESUMO
Background: Emerging evidence suggests that metabolism plays important roles in the initiation and progression of colon cancer (CC) and the outcomes of CC patients. Long non-coding RNAs (lncRNA) are key regulators of regulatory molecules linking to a wide variety of cancer cellular functions. This study aims to develop a metabolic lncRNA signature to help better predict prognosis for CC patients. Methods: In the current study, the transcriptome data and clinical data of CC was downloaded from The Cancer Genome Atlas (TCGA). Metabolism-related gene sets were downloaded from the Molecular Signatures Database (MSigDB). Differential lncRNAs related to metabolism was obtained by performing the correlations between differential expression profile of metabolic genes and lncRNAs. To construct a prognostic model of CC based on metabolism-related lncRNAs, we divided patients, whose clinical data were available, into a training set and a validation set at a ratio of 7:3. The prognostic metabolism related-lncRNA signature was established using the training set by univariate and multivariate Cox regression analysis, and the validation set was used to test the capacity of the prognostic model. The correlation between risk score and clinicopathological features, immune function GO and KEGG analysis was investigated using the entire set. Finally, GSEA pathway enrichment analysis was carried out on the entire set samples for the high- and low- risk groups. Results: We identified 604 differential lncRNAs and 252 genes related to metabolism. After univariate and multivariate Cox regression analysis, four lncRNAs were finally identified to build a signature, which was verified the effectiveness by the TCGA validation set. The multivariate Cox regression analysis showed that the risk score, age of diagnosis and T stage were independent prognostic factor for CC patients. It is shown that some immunopathogenesis, GO items and KEGG pathways demonstrated difference between high- and low- risk group. Conclusions: We developed a four-metabolism related-lncRNA signature for prognostic prediction of CC, which may help select high-risk subpopulation patients who require more aggressive therapy or intervention.
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Whether chronic exposure to environmental doses of polycyclic aromatic hydrocarbons (PAHs) can lead to neurotoxic effects is still unclear. Hence, the neurotoxic effects of perinatal and juvenile exposure to 16 priority-controlled PAHs were investigated. The mice were treated with 0, 0.5, 18.75, 50, 1875 µg/kg/day of PAHs corresponding to various population exposure concentrations from gestation to postnatal day 60. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and hippocampal and cortical neurotransmitter levels were determined using liquid chromatography-tandem mass spectrometry. Typical indicators or outcome of neurotoxicity, including, spatial learning and memory ability, hippocampal long-term potentiation (LTP) and dendritic spine density were evaluated via Morris water maze tests, electrophysiological experiments and Golgi-Cox assays, respectively. The results showed that exposure to different levels of PAH could not increase oxidative DNA damage level. Mice exposed to 0.5, 50 and 1875 µg/kg/day PAHs had significantly longer escape latency than the control group only on the 1st day (p < 0.05). The number of platform crossings and the time spent in target quadrant were similar between the control and the PAHs-exposed mice. Compared with the control mice, only those exposed to 50 µg/kg/day PAHs had significantly lower LTP in hippocampal CA1 region and dendritic spine density in hippocampal DG region (p < 0.05). Except for serotonin, no significant difference in hippocampal and cortical neurotransmitter concentrations was observed between the control and PAHs-exposed groups. Taken together, perinatal and juvenile exposure to environmental doses of PAHs had no profound effect on spatial learning and memory abilities, hippocampal LTP, dendritic spines density, and neurotransmitter levels. These unexpected findings were quite different from previous in vivo studies which commonly used 2-3 orders of magnitude higher PAHs doses to treat animals. Thus, the environmental dose is a crucial reference for future toxicological research to reveal the actual toxic mechanisms and human health effects of PAHs exposure.
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Venenos , Hidrocarbonetos Policíclicos Aromáticos , 8-Hidroxi-2'-Desoxiguanosina , Animais , Feminino , Camundongos , Neurotransmissores , Estresse Oxidativo , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , GravidezRESUMO
Importance: Safe and effective prophylactic therapies for radiation-induced dermatitis (RID) remain an unmet need. Objective: To determine if epigallocatechin-3-gallate (EGCG) solution reduces the incidence of RID in patients undergoing radiotherapy after breast cancer surgery. Design, Setting, and Participants: This phase 2 double-blind, placebo-controlled randomized clinical trial enrolled 180 patients with breast cancer receiving postoperative radiotherapy at Shandong Cancer Hospital and Institute in Shandong, China, between November 2014 and June 2019. Data analysis was performed from September 2019 to January 2020. Interventions: Participants were randomly assigned (2:1) to receive either EGCG solution (660 µmol/L) or placebo (0.9% NaCl saline) sprayed to the whole radiation field from day 1 of the radiation until 2 weeks after radiation completion. Main Outcomes and Measures: The primary end point was incidence of grade 2 or worse RID, defined by the Radiation Therapy Oncology Group scale. The secondary end points included RID index (RIDI), symptom index, changes in the skin temperature measured by infrared thermal images, and safety. Results: A total of 180 eligible patients were enrolled, of whom 165 (EGCG, n = 111; placebo, n = 54) were evaluable for efficacy (median [range] age, 46 [26-67] years). The occurrence of grade 2 or worse RID was significantly lower (50.5%; 95% CI, 41.2%-59.8%) in the EGCG group than in the placebo group (72.2%; 95% CI, 60.3%-84.1%) (P = .008). The mean RIDI in the EGCG group was significantly lower than that in the placebo group. Furthermore, symptom indexes were significantly lower in patients receiving EGCG. Four patients (3.6%) had adverse events related to the EGCG treatment, including grade 1 pricking skin sensation (3 [2.7%]) and pruritus (1 [0.9%]). Conclusions and Relevance: In this randomized clinical trial, prophylactic use of EGCG solution significantly reduced the incidence and severity of RID in patients receiving adjuvant radiotherapy for breast cancer. It has the potential to become a new choice of skin care for patients receiving radiotherapy. Trial Registration: ClinicalTrials.gov Identifier: NCT02580279.
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Neoplasias da Mama , Catequina , Radiodermite , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Catequina/análogos & derivados , Catequina/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Radiodermite/etiologia , Radiodermite/prevenção & controle , Resultado do TratamentoRESUMO
OBJECTIVE: The purpose of this study was to evaluate the potential of CYFRA 21-1 (CYFRA) and CEA as a prognostic marker in patients with undifferentiated nasopharyngeal carcinoma (NPC). METHODS: From March 2004 to February 2008, 62 patients with newly diagnosed, undifferentiated NPC were treated in our department. Their clinocopathological data were analyzed retrospectively. All patients received intensity-modulated radiotherapy using 6 MV X-rays, and serum CYFRA and CEA before and after radiotherapy were assayed. The association among the long-term follow-up results and age, sex, smoke, TNM stage, chemotherapy, CEA, CYFRA and the changes in any direction of serum CYFRA and CEA were determined. RESULTS: Patients with low pre-RT level (≤ 2.49 µg/L) of CYFRA had a significantly better overall survival (OS) than patients with high level (> 2.49 µg/L,OR = 8.555, P = 0.029). N classification and T classification were positively associated with the prediction of progression free survival (OR = 4.054, P = 0.001;OR = 3.873, P = 0.001). But there was no significant association between the rest predictors (age, sex, CEA, post-RT CYFRA, chemotherapy and a radiation-induced decrease in serum markers) and the survival or recurrence rate by multivariate analysis. CONCLUSIONS: The results of the present study show that pre-RT serum CYFRA level is a valuable factor for predicting long-term survival in patients with undifferentiated nasopharyngeal carcinoma. More aggressive treatment may be given to those patients with a high serum CYFRA level.
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Antígenos de Neoplasias/sangue , Antígeno Carcinoembrionário/sangue , Carcinoma/sangue , Carcinoma/radioterapia , Queratina-19/sangue , Neoplasias Nasofaríngeas/sangue , Neoplasias Nasofaríngeas/radioterapia , Adolescente , Adulto , Idoso , Carcinoma/patologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Radioterapia de Intensidade Modulada , Estudos Retrospectivos , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: Previous analysis of the study (NCT02577393) had demonstrated the application of epigallocatechin-3-gallate (EGCG) could be safe and effective in the prevention and treatment of acute radiation esophagitis in patients with advanced lung cancer. EGCG seemed to improve the response rate of small cell lung cancer (SCLC) to radiotherapy in a subgroup analysis. This research continued to analyze the impact of EGCG application on cancer-radiation efficacy and patient survival. METHODS: All patients with SCLC in the NCT02577393 study were included. Patients were randomized into EGCG group or conventional therapy group as protocol. The primary endpoints of the study were radiation response rate and progression-free survival (PFS). Overall survival (OS) and the efficacy of EGCG in the treatment of esophagitis were assessed as secondary endpoints. RESULTS: A total of 83 patients with lung cancer in the NCT02577393 study were screened, and all 38 patients with SCLC were eligible for analysis. No significant differences with regard to baseline demographic and clinical characteristics were observed between the two groups. The objective response rate (ORR) was higher than that of conventionally treated patients (84.6 vs 50%, P = 0.045), while the median PFS and OS were not significantly prolonged. At data cut-off (1 January 2021), 5-year PFS was 33% with EGCG versus 9.3% with conventional treatment, and 5-year OS was 30.3% versus 33.3%, respectively. The mean adjusted esophagitis index and pain index of patients with EGCG application were lower than conventional treatment (5.15 ± 2.75 vs 7.17 ± 1.99, P = 0.030; 8.62 ± 5.04 vs 15.42 ± 5.04, P < 0.001). CONCLUSION: The study indicates EGCG may alleviate some esophagitis-related indexes in SCLC patients exposed to ionizing radiation without reducing survival. However, this conclusion should be confirmed by further studies with large sample size.
RESUMO
PURPOSE: This study aimed to compare erlotinib (E) and etoposide/cisplatin (EP) with concurrent radiation therapy (RT) for patients with stage IIIA/B unresectable advanced non-small cell lung cancer with activating epidermal growth factor receptor mutation (EGFRm+). METHODS AND PATIENTS: This was a multicenter, randomized, open-label, phase 2 trial conducted across 19 institutions in China (December 2012 to January 2016). Enrolled patients were randomized (1:1) to E + RT (oral erlotinib 150 mg/d for 2 years or until disease progression or intolerable toxicity and RT 200 cGy/d, 5 d/wk for 6 weeks from the first day of erlotinib) or EP + RT (etoposide 50 mg/m2 intravenously on days 1-5 and 29-33; cisplatin 50 mg/m2 intravenously on days 1, 8, 29 and 36; and RT as for E + RT). The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate and safety. RESULTS: Two hundred fifty-two patients were screened, and 20 patients with EGFRm+ in each group received the allocated E + RT or EP + RT treatment. Patient characteristics were well balanced between groups. Compared with EP + RT, median PFS with E + RT was significantly longer (24.5 vs 9.0 months [hazard ratio, 0.104; 95% confidence interval, 0.028-0.389; P < .001]). Objective response rate in the E + RT and EP + RT groups was 70% and 61.9%, respectively (P = .744). The incidence of adverse events (any grade) was similar between E + RT and EP + RT groups (88.9% and 84.2%). CONCLUSIONS: The primary endpoint of PFS was met, and the data showed that E + RT might provide PFS improvement compared with EP + RT, with similar tolerability. However, definitive statements regarding the efficacy of concurrent E + RT in patients with unresectable stage III non-small cell lung cancer with activating EGFRm+ cannot be made, and slow patient accrual will likely make it infeasible to conduct a phase 3 study.
Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas , Quimiorradioterapia/métodos , Genes erbB , Neoplasias Pulmonares , Mutação , Adulto , Idoso , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , China , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Intervalos de Confiança , Esquema de Medicação , Epirubicina/administração & dosagem , Epirubicina/efeitos adversos , Cloridrato de Erlotinib/administração & dosagem , Cloridrato de Erlotinib/efeitos adversos , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Radiossensibilizantes/administração & dosagem , Radiossensibilizantes/efeitos adversos , Radioterapia , Dosagem RadioterapêuticaRESUMO
The purpose of this study was to evaluate the potential of serum CYFRA21-1 and carcinoembryonic antigen (CEA) as prognostic markers in patients with undifferentiated nasopharyngeal carcinoma. Sixty-one patients who received definitive radiotherapy/chemoradiotherapy were analysed retrospectively. We investigated the association of the follow-up results with pretreatment level, post-treatment level and change of serum CYFRA21-1 and CEA, respectively. Patients with low pretreatment CYFRA21-1 had a significantly better overall survival. There were no significant associations among the remaining serum markers, and the survival and recurrence rates on multivariate analysis. The present study shows that pretreatment CYFRA21-1 level is a potential factor for predicting long-term survival.
Assuntos
Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , Queratina-19/sangue , Neoplasias Nasofaríngeas/sangue , Adulto , Antígeno Carcinoembrionário/sangue , Diferenciação Celular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/patologia , Prognóstico , Estudos RetrospectivosRESUMO
Acute radiation-induced esophagitis (ARIE) is among the most serious form of toxicities associated with definitive radiotherapy or chemoradiotherapy used for treatment of patients with esophageal cancer. Our preliminary phase I and II trials of lung cancer patients who received radiotherapy indicated epigallocatechin-3-gallate (EGCG) as a promising therapeutic option against ARIE. Therefore, we conducted a prospective phase II study to validate the efficacy and safety of EGCG in the treatment of ARIE. The patients who received chemoradiotherapy or definitive radiotherapy for treatment of esophageal cancer in the Shandong Cancer Hospital and Institute in China were enrolled for the present study. EGCG (440 µM) was administered with first onset of ARIE and then at weeks after final radiotherapy. The patients were monitored every week for dysphagia, Radiation Therapy Oncology Group (RTOG) score, and esophagitis-related pain. Moreover, tumor response and the effect on survival following the treatment were also evaluated. Comparison of the RTOG score in the first, second, third, fourth, fifth, and even sixth week after EGCG prescription and the first and second week after radiotherapy with baseline indicates a significant reduction. The tumor response rate was 86.3%. The overall survival rate in 1, 2, and 3 years was found to be 74.5%, 58%, and 40.5%. Oral administration of EGCG solution seems to be feasible for treating ARIE in patients with esophageal cancer who receive radiation therapy. EGCG might be an ARIE-reliever without compromising the efficacy of radiation therapy. A randomized study with a control group is needed for further evaluation.
Assuntos
Catequina/análogos & derivados , Quimiorradioterapia/efeitos adversos , Neoplasias Esofágicas/terapia , Esofagite/tratamento farmacológico , Lesões por Radiação/tratamento farmacológico , Adulto , Idoso , Catequina/uso terapêutico , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND AND PURPOSE: This trial investigated whether epigallocatechin-3-gallate (EGCG), a radioprotector, could be effective in the prevention and treatment of acute radiation-induced esophagitis (ARIE). METHODS AND MATERIALS: This is a phase II study of EGCG combined with chemoradiation in unresectable stage III non-small-cell lung cancer or limited stage small cell lung cancer. Patients were randomized into a prophylactic EGCG group (arm A), a therapeutic EGCG group after the occurrence of esophagitis (arm B) or conventional therapy group (arm C). Esophagitis grades, pain and dysphagia scores were recorded weekly. Adjusted esophagitis index (AEI), pain index (API) and dysphagia index (ADI) were calculated to reflect changes in esophagitis grade, pain score and dysphagia score throughout treatment. RESULTS: A total of 83 patients were eligible for toxicity analysis (arm A vs arm B vs arm C: Nâ¯=â¯28:27:28). There was no significant difference in the baseline characteristics among three arms of the patients. The difference in the maximum esophagitis grade among three groups was statistically significant (Pâ¯=â¯0.004). The maximum ARIE for patients with EGCG was significantly lower than for those with conventional therapy. The mean AEI of arm A was lower than that of arm B, while the mean AEI of arm C was the highest (arm A vs arm B, Pâ¯=â¯0.028; arm B vs arm C, Pâ¯=â¯0.002). Furthermore, API and ADI were significantly lower in patients receiving EGCG than in conventionally treated patients. CONCLUSION: The application of EGCG could effectively alleviate acute radiation esophagitis in advanced lung cancer without obvious side effects. Prophylactic application of EGCG had a slight advantage over therapeutic use in treatment of acute esophagitis.