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The objective of this study was to develop a nomogram including parameters assessed by 18F-FDG PET/CT and clinical parameters for patients with diffuse large B-cell lymphoma (DLBCL) to predict progression-free survival (PFS). A total of 181 patients with pathologically diagnosed DLBCL at Sichuan Cancer Hospital and Institute from March 2015 to December 2020 were enrolled in this retrospective study. The area under the receiver operating characteristic (ROC) curve (AUC) was used to calculate the optimal cutoff values of the semiquantitative parameters (SUVmax, TLG, MTV, and Dmax) for PFS. A nomogram was constructed according to multivariate Cox proportional hazards regression. The predictive and discriminatory capacities of the nomogram were then measured using the concordance index (C-index), calibration plots, and Kaplan-Meier curves. The predictive and discriminatory capacities of the nomogram and the International Prognostic Index of the National Comprehensive Cancer Network (NCCN-IPI) were compared via the C-index and AUC. Multivariate analysis demonstrated that male gender and pretreatment Ann Arbor stage III-IV, non-GCB, elevated lactate dehydrogenase (LDH), number of extranodal organ involvement (Neo)>1, MTV≥152.8 cm3, and Dmax ≥53.9 cm were associated with unfavorable PFS (all p<0.05). The nomogram, including gender, Ann Arbor stage, pathology type, Neo, LDH levels, MTV, and Dmax, showed good prediction accuracy, with a C-index of 0.760 (95% CI: 0.727-0.793), which was higher than that of NCCN-IPI (0.710; 95% CI: 0.669-751). The calibration plots for 2-year demonstrated good consistency between the predicted and observed probabilities for survival time. We established a nomogram including MTV, Dmax, and several clinical parameters to predict the PFS of patients with DLBCL, and the nomogram showed better predictability and higher accuracy than NCCN-IPI.
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Oxidative stress (OS) is a chemical imbalance between an oxidant and an antioxidant, causing damage to redox signaling and control or causing molecular damage. Unbalanced oxidative metabolism can produce excessive reactive oxygen species (ROS). These excess ROS can cause drastic changes in platelet metabolism and further affect platelet function. It will also lead to an increase in platelet procoagulant phenotype and cell apoptosis, which will increase the risk of thrombosis. The creation of ROS and subsequent platelet activation, adhesion, and recruitment are then further encouraged in an auto-amplifying loop by ROS produced from platelets. Meanwhile, cancer cells produce a higher concentration of ROS due to their fast metabolism and high proliferation rate. However, excessive ROS can result in damage to and modification of cellular macromolecules. The formation of cancer and its progression is strongly associated with oxidative stress and the resulting oxidative damage. In addition, platelets are an important part of the tumor microenvironment, and there is a significant cross-communication between platelets and cancer cells. Cancer cells alter the activation status of platelets, their RNA spectrum, proteome, and other properties. The "cloaking" of cancer cells by platelets providing physical protectionï¼avoiding destruction from shear stress and the attack of immune cells, promoting tumor cell invasion.We explored the vicious circle interaction between ROS, platelets, and cancer in this review, and we believe that ROS can play a stimulative role in tumor growth and metastasis through platelets.
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Plaquetas , Neoplasias , Humanos , Plaquetas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo , Antioxidantes/metabolismo , Oxirredução , Neoplasias/metabolismo , Microambiente TumoralRESUMO
BACKGROUND: Epithelial ovarian cancer (EOC) stands up for about 90% of ovarian cancer cases, which is the frequent cause of death among women. LncRNAs are involved in progression of EOC. Meanwhile, lncRNA SNHG17 was upregulated in EOC, while the detailed function of SNHG17 in EOC remains unclear. METHODS: Protein and mRNA levels were assessed by western blot and RT-qPCR, respectively. The function of SNHG17 in EOC cells was tested by CCK-8, Ki-67 staining, flow cytometry and transwell assay. Dual luciferase was applied for assessing the relation among SNHG17, miR-485-5p and AKT1. Furthermore, in vivo experiments were applied to test the impact of SNHG17 in EOC. RESULTS: SNHG17 knockdown reduced the proliferation and promoted the apoptosis of EOC cells. Consistently, si-SNHG17 obviously reduced the invasion and epithelial-to-mesenchymal transition (EMT) process of EOC cells. MiR-485-5p was proved to be the target miRNA of SNHG17, and SNHG17 negatively regulated the level of miR-485-5p. MiR-485-5p inhibitor significantly abolished the anti-tumor impact of si-SNHG17 on EOC. AKT1 was identified to be targeted by miR-485-5p, and miR-485-5p negatively modulated AKT1 and p-mTOR levels. Moreover, miR-485-5p mimics reduced the proliferation, migration and promoted the apoptosis of EOC cells via targeting AKT1. Furthermore, si-SNHG17 markedly suppressed EOC growth in vivo. CONCLUSION: SNHG17 silencing inhibits the development of EOC via regulation of miR-485-5p/AKT1 axis. Thus, our study might supply a novel strategy against EOC.
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MicroRNAs , Neoplasias Ovarianas , RNA Longo não Codificante , Feminino , Humanos , Carcinoma Epitelial do Ovário/genética , RNA Longo não Codificante/genética , Carcinogênese/genética , Transformação Celular Neoplásica , Neoplasias Ovarianas/genética , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-aktRESUMO
Extracellular vesicles (EVs) are implicated in myocardial ischemia/reperfusion (I/R) injury as modulators by shuttling diverse cargoes, including microRNAs (miRNAs). The current study was initiated to unravel the potential involvement of plasma-derived EVs carrying miR-130a-3p on myocardial I/R injury. Rats were induced with moderate endoplasmic reticulum stress, followed by isolation of plasma-derived EVs. Then, an I/R rat model and hypoxia/reoxygenation (H/R) cardiomyoblast model were established to simulate a myocardial I/R injury environment where miR-130a-3p was found to be abundantly expressed. miR-130a-3p was confirmed to target and negatively regulate autophagy-related 16-like 1 (ATG16L1) in cardiomyoblasts. Based on a co-culture system, miR-130a-3p delivered by EVs derived from plasma protected H/R-exposed cardiomyoblasts against H/R-induced excessive cardiomyoblast autophagy, inflammation, and damage, improving cardiac dysfunction as well as myocardial I/R-induced cardiac dysfunction and tissue injury. The mechanism underlying the functional role of EVs-loaded miR-130a-3p was found to be dependent on its targeting relation with ATG16L1. The protective action of EV-carried miR-130a-3p was further re-produced in a rat model serving as in vivo validation as evidenced by improved cardiac function, tissue injury, myocardial fibrosis, and myocardial infarction. Collectively, miR-130a-3p shuttled by plasma-derived EVs was demonstrated to alleviate excessive cardiomyoblast autophagy and improve myocardial I/R injury.
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Vesículas Extracelulares , MicroRNAs , Traumatismo por Reperfusão Miocárdica , Traumatismo por Reperfusão , Animais , Apoptose , MicroRNAs/genética , Traumatismo por Reperfusão Miocárdica/genética , Ratos , Transdução de Sinais , Proteínas de Transporte VesicularRESUMO
Although the N6 -methyladenosine (m6 A) modification is the most prevalent RNA modification in eukaryotes, the global m6 A modification landscape and its molecular regulatory mechanism in response to drought stress remain unclear. Transcriptome-wide m6 A methylome profiling revealed that m6 A is mainly enriched in the coding sequence and 3' untranslated region in response to drought stress in apple, by recognizing the plant-specific sequence motif UGUAH (H=A, U or C). We identified a catalytically active component of the m6 A methyltransferase complex, MdMTA. An in vitro methyl transfer assay, dot blot, LC-MS/MS and m6 A-sequencing (m6 A-seq) suggested that MdMTA is an m6 A writer and essential for m6 A mRNA modification. Further studies revealed that MdMTA is required for apple drought tolerance. m6 A-seq and RNA-seq analyses under drought conditions showed that MdMTA mediates m6 A modification and transcripts of mRNAs involved in oxidative stress and lignin deposition. Moreover, m6 A modification promotes mRNA stability and the translation efficiency of these genes in response to drought stress. Consistently, MdMTA enhances lignin deposition and scavenging of reactive oxygen species under drought conditions. Our results reveal the global involvement of m6 A modification in the drought response of perennial apple trees and illustrate its molecular mechanisms, thereby providing candidate genes for the breeding of stress-tolerant apple cultivars.
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Secas , Malus , Cromatografia Líquida , Regulação da Expressão Gênica de Plantas , Lignina , Malus/genética , Estresse Oxidativo , Melhoramento Vegetal , Estabilidade de RNA , Estresse Fisiológico/genética , Espectrometria de Massas em Tandem , Transcriptoma/genéticaRESUMO
The induction of embryogenic calli plays a vital role in the genetic transformation and regeneration of rice (Oryza sativa L.). Despite progress in rice tissue culture, the molecular mechanisms of embryogenic callus induction remain unknown. In this study, gene expression profiles associated with calli were comprehensively analyzed during callus induction of japonica rice 'Yunyin'. We first confirmed that NMB medium with 24 h of light and 0 h of dark (NMB-L) was the optimal condition for 'Yunyin' callus induction, while J3 medium with 0 h of light and 24 h of dark (J3-D) was the worst condition. After transcriptome analysis, 33,597 unigenes were assembled, among which we identified 6,063 DEGs (Differentially Expressed Genes) related to media and seven DEGs related to photoperiod. Phenylpropanoid biosynthesis, plant hormone signal, and starch and sucrose metabolism were the top three pathways affected by media, while the circadian rhythm-plant pathway was associated with photoperiod. Furthermore, we identified two candidate genes, Os01g0965900 and Os12g0555200, affected by both medium and photoperiod. Statistical analysis of RNA-seq libraries showed that the expression levels of these two genes in J3-D calli were over 2.5 times higher than those in NMB-L calli, which was further proved by RT-qPCR analysis. Based on FPKM (Fragments Per Kilobase of transcript Per Million mapped reads), unigenes belonging to the NMB-L group were mainly assigned to ribosome, carbon metabolism, biosynthesis of amino acids, protein processing in endoplasmic reticulum, and plant hormone signal transduction pathways. We transformed Os12g0555200Nip and Os12g05552009311 into 'Nipponbare' calli and observed their effects on the growth and development process of rice calli using TEM (Transmission Electron Microscopy) and SEM (Scanning Electron Microscopy). Observations showed that Os12g05552009311 was more disadvantageous to rice callus growth than Os12g0555200Nip. Our results reveal that the Os12g0555200, identified from transcriptomic profiles, has a negative influence during 'Yunyin' callus induction. Supplementary information: The online version contains supplementary material available at 10.1007/s11032-022-01283-y.
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Multisystemic Therapy® (MST) and Functional Family Therapy (FFT) are two widely disseminated evidence-based family-based treatments for substance abusing and delinquent adolescents. This mixed-method study examined common implementation problems in midtreatment in MST and FFT. A convenience sample of experienced therapists (20 MST, 20 FFT) and supervisors (10 MST, 10 FFT) from dissemination sites across the United States participated in semistructured telephone interviews. Participants identified retrospectively serious midtreatment process problems they perceived as threats to treatment success. Coders extracted descriptions of problems from interview transcripts and coded them into 12 categories that fell into five major themes: engaging families in treatment; difficulties implementing strategies; family relational and communication problems; complications external to therapy; and youth problem behavior. Analyses examined caregiver, therapist, and youth variables as predictors of these common midtreatment problems and whether treatment outcomes varied depending on the type of problem, therapy model, and race/ethnic match of therapist and family. MST and FFT therapists and supervisors identified many similar problems. There were, however, model-specific differences consistent with differing features of the models (e.g., FFT participants identified more family relational problems and fewer follow-through problems than their MST counterparts). Results underscore the need to consider both common and specific factors in treatment process.
La terapia multisistémica (Multisystemic Therapy®, MST) y la terapia familiar funcional (Functional Family Therapy, FFT) son dos tratamientos factuales familiares ampliamente difundidos para adolescentes con problemas de abuso de sustancias y delincuencia. Este estudio de métodos combinados analizó los problemas de implementación comunes a mediados del tratamiento en la MST y la FFT. Una muestra de conveniencia de terapeutas experimentados (20 MST, 20 FFT) y supervisores (10 MST, 10 FFT) de centros de difusión de todo EE. UU. participaron en entrevistas telefónicas semiestructuradas. Los participantes reconocieron retrospectivamente graves problemas en el proceso a mediados del tratamiento que percibieron como amenazas para el éxito del tratamiento. Los codificadores extrajeron las descripciones de problemas de las transcripciones de las entrevistas y los codificaron en 12 categorías que comprendían cinco temas principales: interés de las familias por el tratamiento; dificultades para implementar estrategias; problemas de comunicación y relacionales con la familia; complicaciones ajenas a la terapia; y comportamiento problemático de los jóvenes. Los análisis examinaron las variables de cuidador, terapeuta y joven como predictores de estos problemas comunes a mediados del tratamiento y si los resultados del tratamiento variaron según el tipo de problema, el modelo de terapia y la coincidencia étnica/racial entre el terapeuta y la familia. Los terapeutas y los supervisores de la MST y la FFT detectaron varios problemas similares. Sin embargo, hubo diferencias específicas de los modelos que coincidieron con las distintas características de los modelos (p. ej.: los participantes de la FFT reconocieron más problemas de relaciones familiares y menos problemas para terminar el tratamiento que sus homólogos de la MST). Los resultados subrayan las necesidad de tener en cuenta tanto los factores comunes como específicos del proceso de tratamiento.
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Terapia Familiar/métodos , Psicoterapia , Adolescente , Atitude do Pessoal de Saúde , Cuidadores , Serviços Comunitários de Saúde Mental , Prática Clínica Baseada em Evidências , Relações Familiares , Feminino , Humanos , Entrevistas como Assunto , Delinquência Juvenil/reabilitação , Masculino , Poder Familiar , Cooperação do Paciente , Comportamento Problema , Estudos Retrospectivos , Transtornos Relacionados ao Uso de Substâncias/terapiaRESUMO
To our knowledge, left ventricular noncompaction (LVNC) and hypertrophic cardiomyopathy (HCM) commonly occur as separate disorders in different patients; however, LVNC associated with HCM, which is called hypertrophic LVNC, is relatively rare.1) Here we report two sporadic cases of hypertrophic LVNC which were diagnosed by echocardiography and cardiac magnetic resonance (CMR).
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Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Miocárdio Ventricular não Compactado Isolado/complicações , Miocárdio Ventricular não Compactado Isolado/diagnóstico por imagem , Adolescente , Adulto , Ecocardiografia , Feminino , Humanos , Imagem Cinética por Ressonância Magnética , MasculinoRESUMO
Typically, cardiac maxomas arise from the interatrial septum at the border of the fossa ovalis in the left atrium, whereas atypical right atrial myxoma, especially with spontaneous rupture, is extremely rare. Here we report the diagnostic evaluation and successful surgical resection of an atypical myxoma with spontaneous rupture arising from the posterior wall of the right atrium in a 34-year-old male.
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Neoplasias Cardíacas/complicações , Ruptura Cardíaca/etiologia , Mixoma/complicações , Adulto , Procedimentos Cirúrgicos Cardíacos/métodos , Diagnóstico Diferencial , Ecocardiografia , Átrios do Coração , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/cirurgia , Ruptura Cardíaca/diagnóstico , Ruptura Cardíaca/cirurgia , Humanos , Imagem Cinética por Ressonância Magnética , Masculino , Mixoma/diagnóstico , Mixoma/cirurgiaRESUMO
BACKGROUND: Current studies have demonstrated the efficacy and safety of laser intervention in the treatment of onychomycosis. The objective of this study was to compare the efficacy of long-pulsed Nd:YAG 1064 nm laser for treatment of toenails onychomycosis with fingernails onychomycosis. METHODS: One hundred and twelve affected fingernails or toenails in 37 patients with onychomycosis were randomized into Group 1 (22 patients with 50 affected fingernails) and Group 2 (15 patients with 62 affected toenails). These patients were further classified into three subgroups (Grade II, III, and IV) according to Scoring Clinical Index of Onychomycosis. All the affected nails were treated with long-pulse Nd:YAG 1064 nm laser intervention, once weekly, for continuous weeks, and were followed up for 24 weeks. RESULTS: The response rates at weeks 8, 16, and 24 were 0, 0 and 52%, respectively, for Group 1, and 10, 32 and 71% for Group 2. The inter-group difference in efficacy was statistically significant (P<0.05). Even in the same subgroup, the response rate of Group 2 was higher than that of Group 1. CONCLUSIONS: The efficacy of long-pulsed Nd:YAG 1064 nm laser intervention against affected toenails is superior to that against fingernails. It is also effective for treatment of onychomycosis with different severity.
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Dermatoses do Pé/terapia , Dermatoses da Mão/terapia , Lasers de Estado Sólido/uso terapêutico , Onicomicose/terapia , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Dermatoses do Pé/patologia , Dermatoses da Mão/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Onicomicose/patologia , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Ursodeoxycholic acid (UDCA) is a fundamental treatment drug for numerous hepatobiliary diseases that also has adjuvant therapeutic effects on certain cancers and neurological diseases. Chemical UDCA synthesis is environmentally unfriendly with low yields. Biological UDCA synthesis by free-enzyme catalysis or whole-cell synthesis using inexpensive and readily available chenodeoxycholic acid (CDCA), cholic acid (CA), or lithocholic acid (LCA) as substrates is being developed. The free enzyme-catalyzed one-pot, one-step/two-step method uses hydroxysteroid dehydrogenase (HSDH); whole-cell synthesis, mainly uses engineered bacteria (mainly Escherichia coli) expressing the relevant HSDHs. To further develop these methods, HSDHs with specific coenzyme dependence, high enzyme activity, good stability, and high substrate loading concentration, P450 monooxygenase with C-7 hydroxylation activity and engineered strain harboring HSDHs must be exploited.
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Urban growth is recognized as the conversion of vegetated surface to built-up surface. However, there is still no consensus about the urbanization-induced dynamic of vegetation greenness in view of existing literatures. In this study, we aimed to empirically investigate whether urban growth mean the loss of vegetation greenness. We selected 340 Chinese cities as the study areas, relied on consistent multi-temporal remotely sensed data and adopted linear regression analysis, annual growth area, Tail-Sen slope and Mann-Kendall models. Results show that although vegetation greening generally lagged behind urban growth in the monitoring period, a tendency of their consistent speeding up can be observed over time. By categorizing four forms and four trends of vegetation greenness dynamics related to urban growth, we revealed the diversity of Chinese cities. The former focused on the velocity of urban growth and vegetation greenness dynamics within newly urbanized area in three phases, i.e., 2003-2008, 2008-2013 and 2013-2018. The latter focused on the interannual trends of vegetation greenness dynamics among the previously existing and newly urbanized areas. The key finding is that, in over 85 % of the cities, we measured an increase of vegetation greenness along with urban growth. In addition, our detailed results allow quantifying the impact of urbanization in Chinese cities on vegetation protection and sustainable development.
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Rectal cancer is a malignant tumor with poor prognosis. Identification of prognostic biomarkers is needed to improve overall survival of rectal cancer patients. Here, we firstly identified miR-20a-5p significantly classifying high-risk group and low-risk group of rectal cancer patients. We also found that several known miRNAs miR-142-5p, miR-486-5p, miR-490-3p and miR-133a-3p played important roles in rectal cancer. Secondly, we constructed and analyzed a rectal cancer-related miRNA-mRNA network. A rectal cancer-related functional module was identified from the miRNA-mRNA network. Survival analysis demonstrated great prognosis capacity of the module to distinguish rectal cancer patients. Thirdly, a rectal cancer-related miRNA-lncRNA network was constructed, which followed power law distribution. Hub miRNAs and lncRNAs of the network were suggested to show significant prognosis ability and be enriched in cancer-related pathways. Fourthly, we constructed a rectal cancer-related ceRNA network and detected several typical lncRNA-miRNA-mRNA crosstalk, such as HAND2-AS1, HAND2 and miR-20a-5p crosstalk and MBNL1-AS1, miR-429 and LONRF2 crosstalk, which were validated to function in improving overall survival of rectal cancer patients. Finally, we identified the regulatory feedback that was constituted by transcriptional factors and lncRNAs, including MEIS1, MEIS2 and multiple lncRNAs. We also demonstrated that these lncRNAs were high related to immune cell infiltration. All these results can help us to uncover the molecular mechanism and provide new light on miRNA-mediated gene crosstalks in rectal cancer.
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OBJECTIVE: To investigate the prognostic value of interim 18F-FDG PET/CT in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 97 patients with pathologically diagnosed DLBCL at Sichuan Cancer Hospital and Institute from March 2015 to June 2020 were enrolled in this retrospective study. Receiver operating characteristic analysis (ROC) was used to calculate the optimum maximum standard uptake value reduction ratio (â³SUVmax%) cut-off value. The prognostic value of â³SUVmax% and Deauville five-point scale (5-PS) in patients with DLBCL was compared, and the determined prognostic factors were analyzed. RESULTS: ROC curve indicated that the optimum â³SUV max% cut-off value was 74.9%. Patients with â³SUVmax%≥74.9% had a lower rate of progression or recurrence than those with â³SUVmax% < 74.9% (both P<0.001). Meanwhile, patients with 5-PS score < 4 also had a lower rate of progression or recurrence than those with 5-PS score≥4 (both P<0.001). â³SUVmax% and 5-PS had high specificity (83.7% vs 83.7%) and negative predictive value (87.3% vs 84.9%), while low sensitivity (56.0% vs 52.2%) and positive predictive value (53.8% vs 50.0%). â³SUVmax% was more sensitive than 5-PS for the corresponding parameters (78.3% vs 76.2%). Univariate analysis showed that Ann Arbor stage, international prognostic index of National Comprehensive Cancer Network (NCCN-IPI), â³SUVmax% and 5-PS were associated with TTP and PFS (all P<0.001). Multivariate analysis showed that â³SUVmax% was an independent predictor of TTP and PFS (P=0.031, P=0.023). CONCLUSION: Both 5-PS and â³SUVmax% can be used to evaluate the prognosis of DLBCL patients, but the predictive value of â³SUVmax% is superior to that of 5-PS.
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Fluordesoxiglucose F18 , Linfoma Difuso de Grandes Células B , Fluordesoxiglucose F18/uso terapêutico , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Prognóstico , Estudos RetrospectivosRESUMO
The tumor microenvironment (TME) has been shown to be involved in angiogenesis, tumor metastasis, and immune response, thereby affecting the treatment and prognosis of patients. This study aims to identify genes that are dysregulated in the TME of patients with colon adenocarcinoma (COAD) and to evaluate their prognostic value based on RNA omics data. We obtained 512 COAD samples from the Cancer Genome Atlas (TCGA) database and 579 COAD patients from the independent dataset (GSE39582) in the Gene Expression Omnibus (GEO) database. The immune/stromal/ESTIMATE score of each patient based on their gene expression was calculated using the ESTIMATE algorithm. Kaplan-Meier survival analysis, Cox regression analysis, gene functional enrichment analysis, and protein-protein interaction (PPI) network analysis were performed. We found that immune and stromal scores were significantly correlated with COAD patients' overall survival (log rank p < 0.05). By comparing the high immune/stromal score group with the low score group, we identified 688 intersection differentially expressed genes (DEGs) from the TCGA dataset (663 upregulated and 25 downregulated). The functional enrichment analysis of intersection DEGs showed that they were mainly enriched in the immune process, cell migration, cell motility, Toll-like receptor signaling pathway, and PI3K-Akt signaling pathway. The hub genes were revealed by PPI network analysis. Through Kaplan-Meier and Cox analysis, four TME-related genes that were significantly related to the prognosis of COAD patients were verified in GSE39582. In addition, we uncovered the relationship between the four prognostic genes and immune cells in COAD. In conclusion, based on the RNA expression profiles of 1091 COAD patients, we screened four genes that can predict prognosis from the TME, which may serve as candidate prognostic biomarkers for COAD.
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BACKGROUND: Interstitial pneumonitis (IP), a fatal complication of DLBCL treatment, can bring great challenges to clinicians. We retrospectively investigated clinical characteristics and risk factors of previous IP patients, and analyzed their survival data. METHODS: 556 DLBCL patients receiving CHOP-like regimens were enrolled between 2013 and 2018 in Sichuan Cancer Hospital. FINDINGS: The IP incidences were 4.9 % (27/556), 1.1 % (2/186), 5.2 % (10/191) and 8.4 % (15/179) in CHOP, R-CHOP and R-CDOP groups respectively (P = 0.005). When IP was diagnosed, monocyte and IL-6 were significantly higher while CD4 and CD4/CD8 significantly lower compared to baseline. 81.5 % (22/27) of IP patients were pathogen-negative with good response to glucocorticoid monotherapy. Only one patient died while the others recovered from IP and subsequently underwent previous chemotherapy. 19.2 % (5/26) of IP patients experienced IP recurrence, likely due to the reason of lower initial dose or faster withdrawal speed of glucocorticoid. Multivariate analysis identified male, in addition to G-CSF, rituximab and pegylated liposomal doxorubicin as risk factors. The 3-year PFS and OS were 74.1 % and 46.9 % respectively for patients with IP. INTERPRETATION: We suggest that IL-6, monocyte and CD4 should be monitored closely, especially in R-CHOP/R-CDOP group. Sufficient initial dose and slow decrease of glucocorticoid based on radiographic remissions were critical strategies to reduce IP recurrence. We speculate that drug-induced immune imbalance could be trigger of developing IP, causing a lower intensity cytokine storm, resulting in a potential immunotherapy. This complication might bring benefit in patients' survival through a mechanism similar to PD-1.
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Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doenças Pulmonares Intersticiais/mortalidade , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Doxorrubicina/análogos & derivados , Feminino , Seguimentos , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Doenças Pulmonares Intersticiais/induzido quimicamente , Doenças Pulmonares Intersticiais/imunologia , Doenças Pulmonares Intersticiais/patologia , Linfoma Difuso de Grandes Células B/imunologia , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Prednisona/administração & dosagem , Prognóstico , Estudos Retrospectivos , Rituximab/administração & dosagem , Taxa de Sobrevida , Vincristina/administração & dosagemRESUMO
BACKGROUND AND PURPOSE: Aberrant lipid metabolism is recognized as a key feature of cancer cells. Our initial research on MS-based analysis of lipids in a multiple myeloma (MM) cell line showed a significant accumulation of lipids in multiple myeloma cells after proteasome inhibition. This finding prompted us to hypothesize that multiple myeloma cell survival depends on the maximal utilization of abnormally accumulated lipids. Therefore, we explored whether lipid metabolism-modulating agents would synergize with proteasome inhibitors. EXPERIMENTAL APPROACH: Lipid accumulation in multiple myeloma cells was measured by MS. Synergism between lipid regulators and proteasome inhibitors was assessed by cell viability and apoptosis. A novel stable derivative of fenofibrate (FCE) was synthesized and used to treat multiple myeloma cells in vitro and in vivo along with the proteasome inhibitor ixazomib. ChIP-seq, western blotting and RT-qPCR were performed to explore the potential mechanism(s) underlying the increase in lipid levels in multiple myeloma cells after proteasome inhibition. KEY RESULTS: Accumulation of lipids in multiple myeloma cells was induced by proteasome inhibition. Lipid-lowering drugs and MG-132 exerted a synergistic effect to kill multiple myeloma cells. FCE showed significant synergistic activity in vitro and in vivo with ixazomib. The abnormal lipid accumulation in multiple myeloma cells that was enhanced by proteasome inhibitors might be due to the elevated SREBP1/2 expression induced by ATF4. CONCLUSIONS AND IMPLICATIONS: Our results provide a proof of principle and support for the further clinical evaluation of the combination of lipid-modulating drugs with proteasome inhibitors in the treatment of multiple myeloma.
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Antineoplásicos , Mieloma Múltiplo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Bortezomib/farmacologia , Linhagem Celular Tumoral , Humanos , Metabolismo dos Lipídeos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/metabolismo , Complexo de Endopeptidases do Proteassoma , Inibidores de Proteassoma/farmacologiaAssuntos
Remodelamento Atrial , Fibrilação Atrial , Diagnóstico por Imagem , Átrios do Coração , HumanosRESUMO
OBJECTIVES: To determine whether the integration platelet features in blood and platelet rich plasma can establish a model to diagnose lung cancer and colon cancer, even differentiate lung malignancy from lung benign diseases. METHODS: 245 individuals including 159 lung cancer and 86 normal participants were divided into the training cohort and testing cohort randomly. Then, 32 colon cancers, 37 lung cancers, and 21 benign patients were enrolled into validate cohort. The whole blood and corresponding platelet rich plasma (PRP) samples from all participants were prospectively collected, and the platelet features were determined. The features which are statistically significant at the univariate analysis in the training cohort and reported significant features were entered the diagnostic model. A receiver operator characteristic (ROC) curve was drawn to evaluate the accuracy of the model in each cohort. RESULTS: In the training cohort, multiple platelet features were significantly different in lung cancer patients, including MPV in whole blood, MPV, and platelet count in PRP and platelet recovery rate (PRR). For the training cohort, the diagnostic model for lung cancer performed well (AUC = 0.92). The probability distribution of lung cancers and controls in testing cohort were also separated well by the diagnostic model (AUC = 0.79). The diagnostic model for colon cancer also performed well (AUC = 0.79). The model also has a potential value in differentiating the lung malignancy from the benign (AUC = 0.69). CONCLUSION: The PRR was first raised and used in the detection of lung cancer. This study identified a diagnostic model based on PRR and other platelet features in whole blood and PRP samples with the potential to distinguish patients with lung cancer or colon cancer from healthy controls. The model could also be used to distinguish between lung cancer from the benign disease.
Assuntos
Plaquetas , Neoplasias Pulmonares , Plasma Rico em Plaquetas , Estudos de Coortes , Humanos , Neoplasias Pulmonares/diagnóstico , Contagem de PlaquetasRESUMO
BACKGROUND: Proton pump inhibitors (PPIs) are an established kind of drugs used to the treatment of most acid-related diseases. Some prospective studies have noticed that PPI use was associated with increased dementia risk. However, the results of those studies were inconsistent and controversial. This meta-analysis aims to determine the association of PPI use and risk of dementia among older people. METHODS: Relevant articles were systematically identified by searching the PubMed, EMBASE, and Cochrane Library databases from inception to February 2018. Cohort studies that reported the risk of dementia or Alzheimer's disease (AD) among PPI users compared with non-PPI users were included. The quality of studies was assessed using the Newcastle-Ottawa Scale (NOS). The publication bias was detected by a funnel plot and Egger test. The meta-analysis will abstract risk estimates including relative risks (RRs), hazard ratios (HRs), and odds ratios (ORs) with a 95% confidence interval (CI) for the associations between PPI use and dementia or Alzheimer's risk. Study-specific results were pooled using a random-effects model. RESULTS: Six cohort studies were selected finally. The pooled RRs of dementia and AD were 1.23 (95% CI: 0.90-1.67) and 1.01 (95% CI: 0.78-1.32), respectively, compared with those of non-PPI use. The Egger test and funnel plot showed no existence of publication bias. Overall, there was no statistically significant association between PPI use and risk of dementia or AD (Pâ>.05). CONCLUSIONS: This meta-analysis suggests that there was no statistical association between PPIs use and increased risk of dementia or AD.