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BACKGROUND: The immune milieu of colorectal cancer is a complex phenomenon. It is imperative to investigate the crucial immune factors that promote the progression of colorectal cancer. Immune suppressor cells are granulocytic myeloid-derived suppressor cells (G-MDSCs). However, they also increased cancer growth in other ways that need to be investigated further. METHODS: Using flow cytometry, we isolated G-MDSCs from colorectal cancer tissues. Ultracentrifugation was used to separate exosomes from the supernatant of G-MDSCs, and western blotting, transmission electron microscopy (TEM), and flow cytometry were used to confirm their presence. RNA sequencing was used to identify unique miRNAs and transcripts, which were subsequently confirmed by RT-qPCR (real-time quantitative real-time PCR). The CCK-8 test was used to determine the rate of proliferation. Lentiviral vectors were employed to manipulate the expression of miRNAs and genes in order to investigate their role in the development of colorectal cancer. RESULTS: Colorectal cancer tissues have been found to contain granulocyte-myeloid-derived suppressor cells (G-MDSCs) that secrete exosomes. These exosomes have been shown to accelerate cancer progression by promoting cell proliferation. Further research has identified microRNA-166-5p as a target from G-MDSC-derived exosomes. This downregulation leads to the inhibition of integral membrane protein 2B (ITM3E) transcription, which in turn activates the PI3K/Akt signaling pathway. This pathway promotes cell proliferation and can be inhibited using deguelin. The accelerated development of colorectal cancer has been further confirmed in mice models. CONCLUSION: The primary results of this work show that exosomes produced from G-MDSCs and the miR-166-5p/ITM3E axis have therapeutic and diagnostic promise in colorectal cancer.
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Neoplasias Colorretais , MicroRNAs , Células Supressoras Mieloides , Animais , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Células Supressoras Mieloides/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Granulócitos , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Proliferação de Células/genéticaRESUMO
BACKGROUND: Currently, the standard treatment for locally advanced cervical cancer is concurrent chemoradiation (CCRT). Forty percent of patients present with disease recurrence. This study aims to investigate the feasibility, safety and efficacy of neoadjuvant chemotherapy (NACT) with weekly cisplatin and paclitaxel (TP) followed by CCRT. METHODS: We are conducting a phase III trial comparing the efficacy and side effects of patients with cervical cancer (FIGO 2018 stage IIB to IVA) who were assigned to four cycles of NACT with cisplatin (40 mg/m2) and paclitaxel (60 mg/m2) weekly followed by CCRT or CCRT alone. In this report, we studied the medium-term effect of 50 patients enrolled in the NACT + CCRT arm. The primary endpoints were the response rate post-NACT and 12 weeks post-CCRT evaluated by MR/CT based on RECIST v 1.1. The secondary endpoints were 3-year OS (overall survival) and PFS (progression-free survival) measured by the Kaplan-Meier method. RESULTS: Among 50 patients enrolled in the NACT + CCRT arm, the complete and partial response rates were 10.4% and 68.8%, post-NACT. Twelve weeks after treatment completion, the complete response rate was 72.0%, whereas the total response rate (complete and partial response) was 90.0%. After a median follow-up of 28 months, the 3-year OS rate was 83.9%, and the 3-year PFS rate was 73.6%. NACT response was related to superior PFS and OS compared with NACT nonresponse (P < 0.01). Late AEs were exiguous, while early AEs mainly included myelosuppression and gastrointestinal AEs. CONCLUSIONS: This study showed a good response rate achieved by dose-dense weekly cisplatin and paclitaxel followed by standard CCRT. The treatment regimen is feasible, as evidenced by the acceptable toxicity of NACT and by the high compliance with radiotherapy. TRIAL REGISTRATION: Protocol version number and date. Chinese clinical trial registry, ChiCTR1900025327; http://www.chictr.org.cn . Registered 24 August 2019. Retrospectively registered, medresman.org.cn/ChiCTR1900025326. The date recruitment began 01-01-2019.
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Cisplatino , Neoplasias do Colo do Útero , Feminino , Humanos , Paclitaxel/efeitos adversos , Terapia Neoadjuvante/métodos , Neoplasias do Colo do Útero/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Recidiva Local de Neoplasia/tratamento farmacológico , Quimiorradioterapia/métodos , Estadiamento de NeoplasiasRESUMO
BACKGROUND: Since the publication of MA-20 and EORTC-22922 trials, chest wall (CW)/ whole breast (WB) irradiation + comprehensive regional nodal irradiation (RNI) with internal mammary node irradiation (IMNI) has been the standard adjuvant treatment for early-stage breast cancer (BC). However, one size does not fit all BC, and the risk of recurrence significantly varies among this patient population. In addition, whether all BC patients presented with one to three positive lymph nodes (pN1) could benefit from IMNI remains controversial. Thus, the optimal adjuvant RNI volume for early-stage BC with T1-2N1 remains undetermined. METHODS: The IMNI PRECISION trial is a single institute, open-labeled, non-inferior, randomized controlled trial. A total of 214 clinically "high risk" BC patients which is characterized as having at least two of the five clinically adverse factors (age ≤ 40, three positive LN, T2 stage, grade 3 and Ki-67 index ≥ 14%), but genomic score "low risk" (the genomic score ≤ 44) N1 breast cancers are randomly assigned to omitting IMNI group (experimental group) or with IMNI (control group) with a 1:1 ratio. The primary endpoint of this trial is event-free survival, and secondary endpoints include overall survival and locoregional recurrence-free survival. DISCUSSION: The IMNI PRECISION design allows promising clinical-genomic model to stratify the individualized risk of developing recurrence and guides the optimal RNI treatment for early-stage (pT1-2N1) BC patients. We anticipate that our results would provide high-level evidence to tailor IMNI according to individualized recurrence risk of BC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT04517266 . Date of registration: August 18, 2020. Status: Recruiting.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Metástase Linfática/radioterapia , Metástase Linfática/patologia , Linfonodos/patologia , Radioterapia Adjuvante/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Ensaios Clínicos Fase II como AssuntoRESUMO
PURPOSE: To develop a weakly supervised deep learning (WSDL) method that could utilize incomplete/missing survival data to predict the prognosis of extranodal natural killer/T cell lymphoma, nasal type (ENKTL) based on pretreatment 18F-FDG PET/CT results. METHODS: One hundred and sixty-seven patients with ENKTL who underwent pretreatment 18F-FDG PET/CT were retrospectively collected. Eighty-four patients were followed up for at least 2 years (training set = 64, test set = 20). A WSDL method was developed to enable the integration of the remaining 83 patients with incomplete/missing follow-up information in the training set. To test generalization, these data were derived from three types of scanners. Prediction similarity index (PSI) was derived from deep learning features of images. Its discriminative ability was calculated and compared with that of a conventional deep learning (CDL) method. Univariate and multivariate analyses helped explore the significance of PSI and clinical features. RESULTS: PSI achieved area under the curve scores of 0.9858 and 0.9946 (training set) and 0.8750 and 0.7344 (test set) in the prediction of progression-free survival (PFS) with the WSDL and CDL methods, respectively. PSI threshold of 1.0 could significantly differentiate the prognosis. In the test set, WSDL and CDL achieved prediction sensitivity, specificity, and accuracy of 87.50% and 62.50%, 83.33% and 83.33%, and 85.00% and 75.00%, respectively. Multivariate analysis confirmed PSI to be an independent significant predictor of PFS in both the methods. CONCLUSION: The WSDL-based framework was more effective for extracting 18F-FDG PET/CT features and predicting the prognosis of ENKTL than the CDL method.
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Aprendizado Profundo , Linfoma Extranodal de Células T-NK , Fluordesoxiglucose F18 , Humanos , Células Matadoras Naturais , Linfoma Extranodal de Células T-NK/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prognóstico , Estudos RetrospectivosRESUMO
Extranodal natural killer/T-cell lymphoma, nasal-type (ENKTL) is a type of rare and distinct entity of non-Hodgkin lymphoma with poor prognosis. It is important to evaluate the early treatment response accurately to decide further treatment strategy. 18F-FDG PET/CT plays an important role in response evaluation and prognostic prediction in some kinds of lymphomas. However, data available regarding patients with ENKTL are limited. Thus, in this prospective study, we analyzed the prognostic value of 18F-FDG PET/CT in ENKTL. Thirty-four patients with newly diagnosed ENKTL were enrolled in this phase 2 study (NCT02825147, July 7, 2016). The patients received pre-, mid-, and end-treatment 18F-FDG PET/CT scans. Deauville score (DS), maximal standardized uptake values (SUVmax), and the change in SUVmax (ΔSUVmax) were recorded for response assessment. The median follow-up period was 42.2 months. The 2-year overall survival (OS) and progression-free survival (PFS) were 82.4% and 73.5%, respectively. Univariate analysis revealed that Ann Arbor stage (P < 0.002), mid-treatment DS (P = 0.005), mid-SUVmax (P = 0.001), mid-∆SUVmax (P = 0.004), end-treatment DS (P < 0.001), and end-SUVmax (P = 0.014) were prognostic factors for OS. Ann Arbor stage (P = 0.001), mid-treatment DS (P = 0.008), mid-SUVmax (P = 0.029), mid-∆SUVmax (P < 0.001), and end-treatment DS (P =0.021) were of prognostic significance for PFS. Multivariate analysis showed that mid-SUVmax (P = 0.042) and DS at the middle (P = 0.050) and end (P = 0.044) of treatment were significant independent predictors of PFS. 18F-FDG PET/CT is useful for predicting the prognosis of ENKTL.
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Linfoma Extranodal de Células T-NK/diagnóstico por imagem , Cavidade Nasal , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Asparaginase/administração & dosagem , Dexametasona/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Radioisótopos de Flúor , Fluordesoxiglucose F18 , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Linfoma Extranodal de Células T-NK/tratamento farmacológico , Linfoma Extranodal de Células T-NK/mortalidade , Linfoma Extranodal de Células T-NK/radioterapia , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Prospectivos , Compostos Radiofarmacêuticos , Radioterapia de Alta Energia , Sensibilidade e Especificidade , Adulto JovemRESUMO
BACKGROUND: The purpose of this study was to analyze the effects of all clinical characteristics on the overall survival time, in order to provide a basis for determining the prognostic factor of patients with pancreatic cancer. METHODS: A total of 103 pancreatic cancer patients were admitted to the Department of Radiotherapy and Chemotherapy of the Ruijin Hospital, Shanghai Jiaotong University School of Medicine, between January 2002 and December 2012. There were 68 men and 35 women; the median age was 62 years. Diagnoses of pancreatic cancer in all patients were confirmed by histopathology, cytology, or clinical diagnosis. The Kaplan-Meier method was performed to calculate the overall survival rate. The log-rank method was used to examine the univariate analysis. The Cox regression model was performed for multivariate analysis. RESULTS: The median survival time was 293 days, the 1-, 2-, and 3-year survival rates were 27.18%, 5.83%, and 1.94%, respectively. Cox regression analysis revealed that age (P=0.015), Karnofsky performance status (PS) (P=0.002), surgical types (P<0.001), and platelet counts (P<0.001) were independent prognostic factors affecting the overall survival of patients with pancreatic cancer. CONCLUSIONS: Pancreatic cancer had a poor prognosis, the general physical condition, age, the availability of radical surgery, and platelet counts were factors influencing the overall survival of patients with pancreatic cancer.
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OBJECTIVE: To explore the combined anti-tumor effect of radiation therapy and gene-targeted suppression of tumor neovasculature in lung adenocarcinoma in vivo, and to explore the feasibility of micro-PET/CT in dynamic evaluation of treatment effectiveness. METHODS: Thirty 5-6-week old male BALB/c nude mice were used in this study. The mouse models of xenotransplanted human lung adenocarcinoma were divided into 5 groups at random, six mice in each group: the control group, radiation treatment alone group and three groups of recombinant baculovirus plus radiation treatment (intratumoral injection, tail vein injection, and intramuscular injection). The tumor volume was measured every 2 days. Growth delay time (GD) and growth inhibition rate was calculated. FDG metabolism was evaluated by micro-PET-CT before and after treatment. The expressions of VEGF, CD31 and Ki-67 were detected by immunohistochemistry (IHC). RESULTS: The tumor growth delay was >12 days, and the tumor inhibition rate was >45% in the recombinant baculovirus combined with radiotherapy groups, significantly higher than that of the radiotherapy alone group (P < 0.05). Immunohistochemical analysis showed that the expressions of VEGF, CD31 and Ki-67 were significantly lower than that in other groups (P < 0.05). The micro-PET-CT assessment showed that the FDG-metabolism in the recombinant baculovirus combined with radiotherapy groups was significantly reduced (P < 0.05), and the SUVmax (FDG metabolism) of transplanted tumors after treatment was also markedly decreased in comparison with that of the control group. The tumor volume after treatment was significantly correlated with SUVmax in the recombinant baculovirus intratumoral injection + radiotherapy group(r = 0.976), recombinant baculovirus intravenous injection + radiotherapy group (r = 0.954), recombinant baculovirus intramuscular injection + radiotherapy group (r = 0.929), and radiotherapy alone group (r = 0.871, P < 0.05). CONCLUSIONS: The recombinant baculovirus containing Egr1 promoter and K5 gene combined with radiotherapy enhances the suppressing effect on the growth of lung adenocarcinoma in the tumor-bearing nude mice. The inducibility of Egr1 promoter by radiation allows the targeting and controllability of treatment. Micro-PET-CT results have a good correlation with the treatment effectiveness. Therefore, it can be used in real-time evaluation of tumor metabolic function in vivo.
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Adenocarcinoma/radioterapia , Proteína 1 de Resposta de Crescimento Precoce/genética , Terapia Genética , Neoplasias Pulmonares/radioterapia , Terapia de Alvo Molecular , Fragmentos de Peptídeos/genética , Plasminogênio/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Animais , Baculoviridae/genética , Linhagem Celular Tumoral , Terapia Combinada , Proteína 1 de Resposta de Crescimento Precoce/fisiologia , Fluordesoxiglucose F18 , Vetores Genéticos , Humanos , Antígeno Ki-67/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Fragmentos de Peptídeos/fisiologia , Plasminogênio/fisiologia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Tomografia por Emissão de Pósitrons , Regiões Promotoras Genéticas , Distribuição Aleatória , Proteínas Recombinantes/genética , Tomografia Computadorizada por Raios X , Carga Tumoral , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
PROPOSE: To evaluate the advantage of the manual adaptive plans comparing to the scheduled plans, and explored clinical factors predicting patients suitable for adaptive strategy. METHODS AND MATERIALS: Eighty two patients with weekly online cone-beam computed tomography (CBCT) were enrolled. The re-CT simulation was performed after 15 fractions and a manual adaptive plan was developed if a significant deviation of the planning target volume (PTV) was found. To evaluate the dosimetric benefit, D98, homogeneity index (HI) and conformity index (CI) for the planning target volume (PTV), as well as D2cc of the bowel, bladder, sigmoid and rectum were compared between manual adaptive plans and scheduled ones. The clinical factors influencing target motion during radiotherapy were analyzed by chi-square test and logistic regression analysis. RESULTS: The CI and HI of the manual adaptive plans were significantly superior to the scheduled ones (P = 0.0002, 0.003, respectively), demonstrating a better dose coverage of the target volume. Compared to the scheduled plans, D98 of the manual adaptive plans increased by 3.3% (P = 0.0002), the average of D2cc to the rectum, bladder decreased 0.358 Gy (P = 0.000034) and 0.240 Gy (P = 0.03), respectively. In addition, the chi-square test demonstrated that age, primary tumor volume, and parametrial infiltration were the clinical factors influencing target motion during radiotherapy. Multivariate analysis further identified the large tumor volume (≥ 50cm3, OR = 3.254, P = 0.039) and parametrial infiltration (OR = 3.376, P = 0.018) as the independent risk factors. CONCLUSION: We found the most significant organ motion happened after 15 fractions during treatment. The manual adaptive plans improved the dose coverage and decreased the OAR doses. Patients with bulky mass or with parametrial infiltration were highly suggested to adaptive strategy during definitive radiotherapy due to the significant organ motion.
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Tomografia Computadorizada de Feixe Cônico , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Neoplasias do Colo do Útero , Humanos , Feminino , Planejamento da Radioterapia Assistida por Computador/métodos , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/patologia , Pessoa de Meia-Idade , Idoso , Adulto , Tomografia Computadorizada de Feixe Cônico/métodos , Radiometria/métodos , Órgãos em Risco/efeitos da radiação , Idoso de 80 Anos ou maisRESUMO
Oxygen and nutrient deprivation are common features of solid tumors. Although abnormal alternative splicing (AS) has been found to be an important driving force in tumor pathogenesis and progression, the regulatory mechanisms of AS that underly the adaptation of cancer cells to harsh microenvironments remain unclear. Here, we found that hypoxia- and nutrient deprivation-induced asparagine endopeptidase (AEP) specifically cleaved DDX3X in a HIF1A-dependent manner. This cleavage yields truncated carboxyl-terminal DDX3X (tDDX3X-C), which translocates and aggregates in the nucleus. Unlike intact DDX3X, nuclear tDDX3X-C complexes with an array of splicing factors and induces AS events of many pre-mRNAs; for example, enhanced exon skipping (ES) in exon 2 of the classic tumor suppressor PRDM2 leads to a frameshift mutation of PRDM2. Intriguingly, the isoform ARRB1-Δexon 13 binds to glycolytic enzymes and regulates glycolysis. By utilizing in vitro assays, glioblastoma organoids, and animal models, we revealed that AEP/tDDX3X-C promoted tumor malignancy via these isoforms. More importantly, high AEP/tDDX3X-C/ARRB1-Δexon 13 in cancerous tissues was tightly associated with poor patient prognosis. Overall, our discovery of the effect of AEP-cleaved DDX3X switching on alternative RNA splicing events identifies a mechanism in which cancer cells adapt to oxygen and nutrient shortages and provides potential diagnostic and/or therapeutic targets.
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Processamento Alternativo , Glioblastoma , Animais , Humanos , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Glioblastoma/patologia , Oxigênio/metabolismo , Isoformas de Proteínas/metabolismo , Splicing de RNA , Fatores de Processamento de RNA/metabolismo , Microambiente TumoralRESUMO
In order to study the characteristics and laws of nanocrack generation and self-healing behavior of asphalt materials under tensile action, the molecular dynamics (MD) method was used to simulate the continuous "tensile failure-self-healing" process, and this study remedies the shortcomings of existing experimental and observational methods. It is found that the MD-reproduced formation process of asphalt binder nanocrack contains four stages: "tensile extension", "nanocrack generation", "crack adding, expanding and penetrating" and "cracking failure". The influence of tensile conditions on the tensile cracking simulation of an asphalt binder model was analyzed, and it was found that low temperature and high loading rate would increase the tensile strength of the asphalt binder model. In addition, the MD-reproduced healing process of asphalt binder nanocracks can be divided into four stages: "surface approach", "surface rearrangement", "surface wetting" and "diffusion", which is similar to the healing process of polymers. Finally, from the perspective of energy change, the change rule of dominant van der Waals energy in the self-healing process was studied. Based on the existing research, the influence of damage degree on the healing performance of asphalt binder and its mechanism were further analyzed. The research results further enrich the theoretical research on microlevel cracking and healing of asphalt materials, and have certain theoretical value for the further development of self-healing asphalt materials.
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A real rejuvenator must have the ability to disaggregate oxidized asphaltene nanoclusters. However, few studies pay attention to the topic, and there is a lack of comparison of the disaggregation ability of different rejuvenators. Thus, the disaggregation ability and regeneration mechanism of three bio-rejuvenators (waste cooking oil (WCO), waste wood oil (WWO), and straw liquefied residue oil (SLRO)) on oxidized asphaltene nanoclusters were studied in this paper. Laboratory tests and molecular dynamics (MD) simulation were used to compare the effectiveness of the three bio-rejuvenators and reveal its corresponding mechanism. It is found that these bio-rejuvenators have a softening effect on aged asphalt binder, but not all of them can disaggregate oxidized asphaltene nanoclusters. The introduction of WWO and WCO can effectively disturb the nanoclusters caused by the increase of polar functional groups during the oxidation process. The effect of WWO is more significant, but neither of them can restore the asphaltene dispersion to the virgin asphalt binder. SLRO has an adverse effect on the disaggregation of oxidized asphaltene nanoclusters. WCO, WWO, and SLRO showed different disaggregation mechanisms, including â³pull-out, intercalation, and compressionâ³, respectively. WCO and WWO can increase the activation energy reduced by aging in a short aging time, and SLRO makes the activation energy lower. Such findings can help enterprises screen more reasonable rejuvenators to facilitate the recycling of reclaimed asphalt pavement (RAP) materials and promote the sustainable development of the construction industry.
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Introduction: Pancreatic cancer is one of the most common malignant tumors and is characterized by high malignancy, occult incidence and poor prognosis. Traditional chemotherapy drugs have limited efficacy and strong side effects. Therefore, there is an urgent need for a better treatment of the malignancy. Methods: The prepared arginine glycine peptide (RGD)-human serum albumin (HSA)-Gemcitabine (GEM)/Curcumin (CUR) nanoparticles (NPs) were characterized for physicochemical properties, stability and in vitro release. Comparisons of HSA-GEM/CUR NPs and RGD-HSA-GEM/CUR NPs regarding tissue distributions and pharmacodynamics were also carried out using mice as the animal models. Results: Transmission electron micrographs showed that RGD peptide-conjugated HSA-NPs had an irregular surface, good dispersion (PDI=0.139±0.03) and a uniform size distribution (Mean PS=115.6±5.7 nm). The ζ-potential was -17.3 mV. As regards in vitro release, non RGD modified NPs showed a faster release rate in 24 hours, yielding a release amount of 75% for GEM and 72% for CUR. RGD-HSA-GEM/CUR NPs exhibited 67% of accumulated release of GEM (63% for CUR) in 24 hours. This may be due to the HSA chain covering the surface of NPs, which hindered the drug release. The cytotoxicity of GEM/CUR co-loaded NPs was significantly higher than that of single-drug NPs (P < 0.05). In vivo study results indicated that RGD-HSA-GEM/CUR NPs had notable targeting effect on subcutaneous tumors, with a potential to actively deliver drugs to tumor tissues. Conclusion: In this study, we prepared RGD-HSA-GEM/CUR NPs that had both good water solubility and tumor-targeting property. The results also showed that the RGD modified NPs had advantages in increasing GEM/CUR concentration at tumor sites and reducing its distribution in peripheral organs.
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Curcumina , Nanopartículas , Neoplasias Pancreáticas , Animais , Linhagem Celular Tumoral , Curcumina/química , Desoxicitidina/análogos & derivados , Portadores de Fármacos/química , Humanos , Camundongos , Nanopartículas/química , Oligopeptídeos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Tamanho da Partícula , Albumina Sérica Humana , Gencitabina , Neoplasias PancreáticasRESUMO
BACKGROUND: Currently, the standard treatment for locally advanced cervical cancer is concurrent chemoradiation (CCRT). The effect of neoadjuvant chemotherapy in advanced cervical cancer is controversial. Studies have shown that the addition of a weekly regimen of neoadjuvant chemotherapy (NACT) followed by CCRT may be superior to a thrice-weekly regimen of NACT and CCRT. Among patients who had not received prior cisplatin, a cisplatin and paclitaxel (TP) regimen resulted in longer overall survival than other regimens. This study aims to investigate the feasibility, safety, and efficacy of NACT with weekly TP followed by CCRT. METHODS: This is a prospective, randomized, open-labeled, multicentered phase III study. Based on a 65% of 2-year disease-free survival (DFS) rate in the CCRT group and 80% of that in NACT followed by CCRT group, and on prerequisite conditions including an 8% loss to follow-up, a two-sided 5% of type I error probability, and an 80% of power, a total of 300 cases were required for enrollment. Patients with IIB-IVA cervical cancer will be randomly allocated in a 1:1 ratio to one of two intervention arms. In the study arm, patients will receive dose-dense cisplatin (40 mg/m2) and paclitaxel (60 mg/m2) weekly for 4 cycles followed by CCRT (45 Gy in 5 weeks concurrent with cisplatin 40 mg/m2 weekly) plus image-guided adaptive brachytherapy (IGBRT). In the control arm, patients will undergo CCRT treatment. The primary endpoint of the study is 2-year disease-free survival (DFS); the secondary endpoints are 5-year overall survival (OS) and disease-free survival (DFS), the response rate 3 months after treatment completion, grade III/IV adverse effects, and quality of life, and potential biomarkers for predicting treatment response will also be studied. DISCUSSION: The data gathered from the study will be used to determine whether NACT with weekly TP followed by CCRT may become an optimized treatment for locally advanced cervical cancer. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900025327. Registered on 24 August 2019. medresman.org.cn ChiCTR1900025326.
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Cisplatino , Neoplasias do Colo do Útero , Protocolos de Quimioterapia Combinada Antineoplásica , Quimiorradioterapia , Ensaios Clínicos Fase III como Assunto , Feminino , Humanos , Estudos Multicêntricos como Assunto , Terapia Neoadjuvante , Estadiamento de Neoplasias , Paclitaxel , Estudos Prospectivos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias do Colo do Útero/patologiaRESUMO
INTRODUCTION: Short course regimen has become the major trend in the field of adjuvant radiotherapy for patients with breast cancer. Hypofractionated radiotherapy (HF-RT) regimen of 40-42.5 Gy in 15-16 fractions has been established as a preferred option for whole breast irradiation. However, few evidences of hypofractionated regional nodal irradiation (RNI), especially involving internal mammary nodes (IMNs), could be available during the era of intensity-modulated radiation therapy (IMRT). Against this background, we design this trial to explore the hypothesis that HF-RT regimen involving RNI (including infraclavicular, supraclavicular nodes and IMNs) will be non-inferior to a standard schedule by using IMRT technique. METHODS AND ANALYSIS: This is an open-label randomised, non-inferior, multicentre phase III trial. Patients with breast cancer with an indication for RNI after breast conserving surgery or mastectomy are randomised at a ratio of 1:1 into the following two groups: hypofractionated regimen of 2.67 Gy for 16 fractions or conventional regimen of 2 Gy for 25 fractions. The dose was prescribed to ipsilateral chest wall or whole breast and RNI (including infraclavicular, supraclavicular nodes and IMNs, lower axilla if indicated). The trial plans to enrol a total of 801 patients and all patients will be treated using IMRT technique. The primary endpoint is 5-year locoregional recurrence. The secondary endpoints include 5-year distant metastasis free survival, invasive recurrence-free survival, overall survival, accumulative acute radiation-induced toxicity and accumulative late radiation-induced toxicity, cosmetic outcomes and quality of life. ETHICS AND DISSEMINATION: The study has been approved by the Ethical Committee of Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine (version 2018-95-3) and approvals from ethical committee of each participating centre have also been obtained. Research findings will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03829553.
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Neoplasias da Mama , Lesões por Radiação , Radioterapia de Intensidade Modulada , Humanos , Feminino , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Mastectomia , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Qualidade de Vida , Recidiva Local de Neoplasia/patologia , China , Lesões por Radiação/etiologia , Adjuvantes Imunológicos , Radioterapia Adjuvante , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto , Ensaios Clínicos Fase III como AssuntoRESUMO
OBJECTIVE: To explore the suitable cases for vaginal cuff brachytherapy (VCB) combined with external beam radiation therapy (EBRT) in the postoperative treatment of cervical cancer. METHODS: We retrospectively analyzed the clinical data of 214 postoperative cervical cancer patients who received radiotherapy from January 2008 to December 2015. Among them, 146 patients received postoperative EBRT, 68 received EBRT plus VCB. There was no statistical difference in clinical and pathological characteristics between these two groups. Those who with negative vaginal cuff underwent supplemented 12-18 Gy/2-3 Fx VCB. Survival analyses were performed using Kaplan-Meier method, and Cox model was used to analyze prognostic factors. RESULTS: The median follow-up was 52 months (9-136 months), and 4-year RFS (recurrence-free survival) was 77%. Among them, 58 patients (27.10%) had local or distant recurrences, 29 (13.55%) in pelvis, six (2.80%) with metastases to para-aortic, 19 (8.88%) with distant metastases (including inguinal lymph nodes) and four (1.87%) with both local and distant recurrences. The postoperative brachytherapy boost did not improve RFS or OS (overall survival) among the investigated subjects, P = 0.77, P = 0.99, respectively. Neither it decreased the local relapse in the pelvis or vaginal cuff, P = 0.56, P = 0.59. Subgroup analyses showed that brachytherapy boost improved RFS in patients who had bulky mass (>4 cm) as well as 1) with deep stromal invasion (>50% stromal invasion), P = 0.012 or 2) received low EBRT dose (≤45 Gy), P = 0.033, and in patients with deep stromal invasion as well as received low EBRT dose (P = 0.018). CONCLUSIONS: We first proposed the case selection model for postoperative EBRT plus VCB. Brachytherapy boost were considered in the setting of postoperative radiotherapy if the patients had at least two out of these following factors: bulky mass, deep stromal invasion and low EBRT dose.
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The presence of hypoxia in solid tumors is considered one of the major factors that contribute to radiation resistance. The aim of the present study was to establish a therapeutic system, which can be controlled by radiation itself, to enhance radiosensitivity. For this purpose, a lentiviral gene therapy vector containing the human inhibitor of growth 4 (ING4) and its upstream promoter, human early growth response factor-1 (EGR1), which possesses the radiation-inducible characteristics to activate the transcription of its downstream genes, was constructed. Downstream fluorescence proteins were investigated to ensure that the EGR1 promoter was induced by irradiation. Furthermore, ING4 open reading frame (ORF) expression was detected by western blotting. The cell cycle was analyzed by fluorescence-activated cell sorting analysis 48 h after the cells were exposed to X-rays ranging between 0 and 8 Gy. In cells stably and transiently transfected with reporter plasmids, the EGR1-driver gene was sensitive to ionizing irradiation. Furthermore, irradiation-induced ING4 gene expression was observed. The enhanced ING4 expression increased the number of cells in the G2/M phase and decreased the proportion of cells in the G1/S phase. Therefore, ING4 expression inhibited cell proliferation and was associated with less colonies being formed. Furthermore, ING4 suppressed hypoxia-inducible factor 1α expression under hypoxic conditions and promoted cell apoptosis. Overall, these results revealed that combining the EGR1 promoter and ING4 ORF using a lentivirus system may be a promising therapeutic strategy with which to enhance radiosensitivity controlled by radiation. However, further studies using in vivo models are required to confirm these findings.
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This work presents a machine learning approach for the computer vision-based recognition of materials inside vessels in the chemistry lab and other settings. In addition, we release a data set associated with the training of the model for further model development. The task to learn is finding the region, boundaries, and category for each material phase and vessel in an image. Handling materials inside mostly transparent containers is the main activity performed by human and robotic chemists in the laboratory. Visual recognition of vessels and their contents is essential for performing this task. Modern machine-vision methods learn recognition tasks by using data sets containing a large number of annotated images. This work presents the Vector-LabPics data set, which consists of 2187 images of materials within mostly transparent vessels in a chemistry lab and other general settings. The images are annotated for both the vessels and the individual material phases inside them, and each instance is assigned one or more classes (liquid, solid, foam, suspension, powder, ...). The fill level, labels, corks, and parts of the vessel are also annotated. Several convolutional nets for semantic and instance segmentation were trained on this data set. The trained neural networks achieved good accuracy in detecting and segmenting vessels and material phases, and in classifying liquids and solids, but relatively low accuracy in segmenting multiphase systems such as phase-separating liquids.
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The diagnostic value of pretreatment 18F-FDG PET/CT in early-stage extranodal natural killer/T-cell lymphoma (ENKTL) is established, but its prognostic value is still unclear. We conducted 18F-FDG PET/CT-based quantitative and qualitative analysis as well as assessed related clinical parameters in 50 patients with recently diagnosed ENKTL and treated with methotrexate, etoposide, dexamethasone, and pegaspargase (MESA)-based therapy. Patients were followed-up for 38.6 ± 17.8 months. Six patients died of tumor-related disease, and six patients presented with persistence or recurrence. The estimates of the 2-year OS and PFS for the patients were 90.0% (SE: 4.0%) and 82.0% (SE: 5.0%), respectively. Survival curves were obtained using Kaplan-Meier analysis and compared using log rank test. Based on signifiacnt results of univariate analysis, we selected Epstein-Barr virus DNA (EB-DNA), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for multivariate analysis. Finally, MTV was found to be the significant independent predictor of both OS (p = .038) and PFS (p = .039).
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Infecções por Vírus Epstein-Barr , Linfoma de Células T , Fluordesoxiglucose F18 , Glicólise , Herpesvirus Humano 4 , Humanos , Células Matadoras Naturais , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Carga TumoralRESUMO
UNLABELLED: The first aim of our study was to compare the role of (18)F-FDG PET/CT with that of CT alone in detecting the primary cause of ascites. A secondary aim was to compare the value of (18)F-FDG PET/CT with that of CT alone in detecting abdominal cavity metastasis. Finally, we analyzed the receiver-operating-characteristic (ROC) curves of maximal standardized uptake values (SUVmax), serum carcinoembryonic antigen, CA19-9, and CA12-5 for differential diagnostic abilities. METHODS: The (18)F-FDG PET/CT scans of 40 patients with ascites of undetermined origin, including 30 patients with malignant diseases and 10 with benign lesions, were reviewed for the presence of ascites. Among the 40 patients, 34 had received their diagnosis by pathologic examination and 6 by clinical follow-up. We also assessed the (18)F-FDG PET/CT scans of 20 healthy volunteers for comparison. All (18)F-FDG PET/CT images were visually interpreted, and the SUVmax was measured. We compared the mean diameter of true-positive lesions with that of false-negative lesions. The diagnostic abilities of SUVmax, serum carcinoembryonic antigen, CA19-9, and CA12-5 were compared using the ROC curve. RESULTS: The sensitivity, specificity, and accuracy of PET/CT in detecting the primary cause of ascites were 63.3% (19/30), 70.0% (7/10), and 65.0% (26/40), respectively, and those of CT alone were 36.7% (11/30), 80% (8/10), and 47.5% (19/40), respectively (sensitivity, P < 0.05). The sensitivity of PET/CT was higher than that of CT alone for detecting abdominal cavity metastasis (86.4% vs. 27.3%, P < 0.01). The SUVmax in patients with malignant primary and metastatic lesions was significantly higher than that in healthy volunteers and in patients with benign ascites (P < 0.05). The mean maximal diameter of false-negative lesions was significantly smaller than that of true-positive lesions (P < 0.05). In ROC analysis, the areas under the curve of SUVmax, serum carcinoembryonic antigen, CA19-9, and CA12-5 were 0.803 (P < 0.01), 0.773 (P < 0.05), 0.552 (P > 0.05), and 0.220 (P < 0.01), respectively. CONCLUSION: (18)F-FDG PET/CT assisted in detecting the original cause of ascites. The differential diagnostic ability of (18)F-FDG PET/CT was superior to that of CT alone, tumor markers, and cytology. More attention should be paid to peritoneal tuberculosis, which can markedly accumulate (18)F-FDG and mimic peritoneal carcinoma.
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Ascite/diagnóstico , Fluordesoxiglucose F18 , Aumento da Imagem/métodos , Tomografia por Emissão de Pósitrons/métodos , Técnica de Subtração , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Ascite/classificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto JovemRESUMO
BACKGROUND: Despite increasing clinical data suggest that internal mammary node (IMN) irradiation would improve local-regional control and overall survival in breast cancer, its role remains controversial due to increased risk of cardiac and pulmonary toxicity. The current study aims to determine the high risk areas of IMN metastases by collecting and analyzing the axial imaging of IMN involvement, in order to optimize IMN delineation for breast cancer. METHODS: Breast cancer patients with IMN involvement were retrospectively identified from single-center database. All available imaging modalities including thoracic CT, breast MRI, ultrasound and PET/CT were used to diagnose IMN metastases. Anatomical characteristics from axial imaging, including distribution of involved ribs and distance from the internal mammary vessels (IMV), were collected for each metastatic IMN. What's more,the natural infiltration tendency of IMNs from IMV was calculated in this study. RESULTS: In total, 83 metastatic IMNs from 70 breast cancer patients (initial diagnosed:34 and recurrence: 36) were located from axial CT image in this study. The second intercostal space was the most likely involved in patients with single(n = 35, 53.0%) and multiple intercostal space (n = 31, 47.0%) involvement. The percentage of including IMN with a 5 mm, 6 mm and 7 mm medial/lateral distance to the IMV were 75.9% (63/83), 89.2.6% (74/83) and 92.3% (77/83) respectively. While in maximal dorsal/ventral distance, nearly 95% of the nodes were encompassed into 6 mm depth to the IMV. Over 65% of IMN adenopathy (32/49,65.3%) were found to have a growth direction close to the sternum. By retrospective reviewing diagnostic reports, MRI demonstrated a high diagnostic performance in diagnosis of IMN disease (90.3%, 28/31), while CT had a higher misdiagnosis rate (22/63, 34.9%). The diagnostic efficiency of IMN could be improved if different methods were combined. CONCLUSIONS: For patients with indications of prophylactic IMN irradiation, a 7 mm medial and 6 mm dorsal distance to the IMV on axial CT would be optimal to cover the clinical volume of IMN; and it would be reasonable to extend clinical tumor volume (CTV) coverage towards sternum for patients with evident IMN disease. Multi-imaging modalities are recommended to improve the diagnostic specificity and sensitivity of IMN metastases.