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1.
Sci Rep ; 14(1): 17417, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39075188

RESUMO

Prolonged disorder of consciousness (DoC) is a rising challenge. Pediatric data on diagnosis and prognosis of prolonged DoC were too limited and heterogeneous, making it difficult to define the natural course and evaluate the prognosis. The present study explored the emergence from the Minimally Conscious State (eMCS) incidence at different months postinjury drawing the natural course, and detected the predictors of the incidence in children with prolonged DoC. A hospital-based prospective cohort study was conducted. Kaplan-Meier curves, as well as univariate and multivariate COX regression analysis, were performed. The study enrolled 383 pediatric DoC individuals, including 220 males (57.4%), with an average age of 3.9 (1.9-7.3) years. The median duration between onset and rehabilitation is 30.0 (21.0-46.0) days. At enrollment, the ratio of vegetative state/unresponsive wakefulness syndrome (VS/WUS) to MCS is 78.9%-21.1%. Traumatic brain injury and infection are the major etiologies (36.8% and 37.1%, respectively), followed by hypoxia cerebral injury (12.3%). For children with prolonged DoC, the cumulative incidence of eMCS at months 3, 6, 12, and 24 was 0.510, 0.652, 0.731, 0.784 VS 0.290, 0.418, 0.539, 0.603 in the traumatic VS non-traumatic subgroup, respectively. For children in a persistent vegetative state (PVS), the cumulative incidence of emergence at months in 3, 6, 12, 24, 36 and 48 was testified as 0.439, 0.591, 0.683, 0.724, 0.743 and 0.743 in the traumatic subgroup, and 0.204, 0.349, 0.469, 0.534, 0.589 and 0.620 in the non-traumatic subgroup. Participants who exhibit any of the following four demographical and/or clinical characteristics-namely, older than 4 years at onset, accepted rehabilitation within 28 days of onset, remained MCS at enrollment, or with etiology of traumatic brain injuries-had a significantly positive outcome of consciousness recovery (eMCS). Moreover, both prolongation of the central somatosensory conductive time (CCT) (level 2) and absence of N20 (level 3) independently predict a negative outcome. In children with prolonged DoC, we found that 12 months postinjury was critical to eMCS, and a preferred timepoint to define chronic vegetative state (VS). The characteristics including age, etiology, time before rehabilitation, consciousness state, and SEP results were useful predictors of conscious recovery.Trial registration Registered 06/11/2018, the registration number is chiCTR1800019330 (chictr.org.cn). Registered prospectively.


Assuntos
Transtornos da Consciência , Estado de Consciência , Estado Vegetativo Persistente , Humanos , Feminino , Masculino , Criança , Pré-Escolar , Transtornos da Consciência/etiologia , Estado de Consciência/fisiologia , Lactente , Estudos Prospectivos , Prognóstico , Estado Vegetativo Persistente/fisiopatologia , Recuperação de Função Fisiológica , Lesões Encefálicas Traumáticas/complicações , Incidência
2.
J Fungi (Basel) ; 10(7)2024 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-39057390

RESUMO

Colletotrichum gloeosporioides is the main pathogen that causes poplar anthracnose. This hemibiotrophic fungus, which can severely decrease the economic benefits and ecological functions of poplar trees, infects the host by forming an appressorium. Hox7 is an important regulatory factor that functions downstream of the Pmk1 MAPK signaling pathway. In this study, we investigated the effect of deleting CgHox7 on C. gloeosporioides. The conidia of the ΔCgHox7 deletion mutant germinated on a GelBond membrane to form non-melanized hyphal structures, but were unable to form appressoria. The deletion of CgHox7 weakened the ability of hyphae to penetrate a cellophane membrane and resulted in decreased virulence on poplar leaves. Furthermore, deleting CgHox7 affected the oxidative stress response. In the initial stage of appressorium formation, the accumulation of reactive oxygen species differed between the ΔCgHox7 deletion mutant and the wild-type control. Moreover, CgHox7 expression was necessary for maintaining cell wall integrity. Considered together, these results indicate that CgHox7 is a transcription factor with crucial regulatory effects on appressorium formation and the pathogenicity of C. gloeosporioides.

4.
Bioresour Technol ; 388: 129773, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37722547

RESUMO

This study explored the mechanisms by which biochar mitigates ammonia inhibition in anaerobic digestion (AD) of swine manure. Findings show 2-8 g/L exogenous ammonia dosages gradually inhibited AD, leading to decreases in the efficiencies of hydrolysis, acidogenesis and methanogenesis by 3.4-70.8%, 6.0-82.0%, and 4.9-93.8%, respectively. However, biochar addition mitigated this inhibition and facilitated methane production. Biochar enhanced microbial activities related to electron transport and extracellular electron transfer. Moreover, biochar primarily enriched Methanosarcina, which, consequently, upregulated the genes encoding formylmethanofuran dehydrogenase and methenyltetrahydromethanopterin cyclohydrolase for the CO2-reducing methanogenesis pathway by 26.9-40.8%. It is believed that biochar mediated direct interspecies electron transfer between syntrophic partners, thereby enhancing methane production under ammonia stress. Interestingly, biochar removal did not significantly impact the AD performance of the acclimated microbial community. This indicated the pivotal role of biochar in triggering methanogen evolution to mitigate ammonia stress rather than the indispensable function after the enrichment of ammonia-resistance methanogen.

5.
Angew Chem Int Ed Engl ; 62(43): e202310225, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37596804

RESUMO

The global demand for intelligent sensing of aromatic amines has consistently increased due to concerns about health and the environment. Efforts to improve material design and understand mechanisms have been made, but highly efficient non-contact sensing with host-guest structures remains a challenge. Herein, we report the first example of non-contact, high-contrast sensing of aromatic amines in a hydrogen-bonded organic framework (HOF) based on a nitro-modified stereo building block. Direct observation of binding interactions of trapped amines is achieved, leading to charge separation-induced emission quenching between host and guests. Non-contact sensing of aniline and diphenylamine is realized with quenching efficiencies up to 91.7 % and 97.0 %, which shows potential for versatile applications. This work provides an inspiring avenue to engineer multifunctional HOFs via co-crystal preparations, thus enriching applications of porous materials with explicit mechanisms.

6.
Jpn J Radiol ; 41(10): 1148-1156, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37266825

RESUMO

PURPOSE: The aim of this study was to evaluate the utility of RAI therapy after reoperation for patients with LN relapse. MATERIALS AND METHODS: We retrospectively evaluated PTC patients who had undergone reoperation due to cervical LN recurrence. We used the chi-square test, Fisher's exact test, Student's t test and the Mann-Whitney U test to compare characteristics between patients retreated with RAI and those who did not receive RAI after reoperation. A multivariate logistic regression model was used to determine the association between RAI and biochemical response. By means of the Kaplan-Meier estimator and a multivariate Cox proportional hazard model, we assessed whether administration of RAI after reoperation is associated with improved prognosis. RESULTS: RAI therapy was closely associated with a superior biochemical response in all selected patients according to both univariate (p = 0.012) and multivariate analyses (p = 0.020). Thirteen of 97 patients developed a second recurrence or progression of structural disease during follow-up. A Kaplan-Meier progression-free survival (PFS) curve showed that high post-retreatment thyroglobulin (Tg) levels (≥ 1 ng/mL) were associated with unfavourable prognosis (p = 0.0172). In the subgroup analysis, univariate analysis revealed that only patients without extranodal invasion who received adjuvant RAI therapy achieved better PFS than those who did not receive RAI therapy (p = 0.0203). Multivariate analysis showed that RAI (p = 0.045) also improved PFS in patients without extranodal invasion. CONCLUSIONS: Adjuvant RAI after reoperation for PTC recurrence/persistence was associated with a favourable biochemical response and tended to increase PFS. Specifically, it was significantly associated with improved PFS only in patients without extranodal extension.


Assuntos
Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/radioterapia , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Reoperação , Radioisótopos do Iodo/uso terapêutico , Estudos Retrospectivos , Tireoidectomia , Recidiva Local de Neoplasia/radioterapia , Linfonodos/patologia
7.
Br J Dermatol ; 188(4): 491-498, 2023 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-36641781

RESUMO

BACKGROUND: Psoriasis can be provoked by both external and internal factors. The effects of environmental factors on psoriasis remain unclear. OBJECTIVES: To investigate the effects of air pollution on outpatient visits for psoriasis. METHODS: A distributed lag nonlinear model following quasi-Poisson regression was used to evaluate the lag effects of air pollutants on psoriasis outpatient visits, adjusting for potential confounders. Stratified analyses were performed to identify potential effect modifications by sex, age and season. RESULTS: In total, 13 536 outpatient visits for psoriasis were recorded in Wuhan, China from 1 January 2015 to 31 December 2019. In the single-pollutant model, exposures to particulate matter (PM) smaller than 2.5 µm (PM2.5), PM smaller than 10 µm (PM10), NO2 and SO2 were found to be significantly associated with increased daily psoriasis outpatient visits. For the largest effects, a 10-µg m-3 increase in concentrations of PM2.5 (lag1), PM10 (lag1), NO2 (lag0) and SO2 (lag3) corresponded to 0.32% [95% confidence interval (CI) 0.01-0.63], 0.26% (95% CI 0.05-0.48), 0.98% (95% CI 0.01-1.96) and 2.73% (95% CI 1.01-4.47) increases in psoriasis outpatient visits, respectively. In the two-pollutant model, only NO2 showed significant and stable effects on the outpatient visits for psoriasis. CONCLUSIONS: Ambient air pollution, especially NO2, appears to be significantly associated with an increased risk of outpatient visits for psoriasis in Wuhan, China. Air pollution control and exposure prevention could be effective measures to relieve the symptoms of psoriasis among these patients.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Ambientais , Humanos , Pacientes Ambulatoriais , Dióxido de Nitrogênio/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Material Particulado/efeitos adversos , Material Particulado/análise , Poluentes Ambientais/análise , China/epidemiologia
8.
Cancer Med ; 12(2): 1204-1216, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35856487

RESUMO

BACKGROUND: Total omentectomy is often performed with gastrectomy as radical surgery for gastric cancer (GC) patients. However, it remains controversial whether GC patients can benefit from omentectomy. The aim of this study was to analyze the incidence and clinical significance of tumor deposits (TDs) in different anatomical subregions of perigastric omentum in GC patients undergoing gastrectomy with total omentectomy. METHODS: From October 2011 to December 2013, 1253 patients who underwent gastrectomy with total omentectomy for GC were retrospective reviewed. The TDs in different anatomical subregions of perigastric omentum were examined. RESULTS: Of 1253 patients, TDs positivity was 11.2%. Tumor deposits in the omentum of greater curvature and in the omentum of lesser curvature were associated with lymphovascular invasion, perineural invasion, advanced tumor node metastasis stages, and unfavorable survival. Besides, TDs in the proximal omentum of greater curvature and in the omentum of lesser curvature correlated with older patients and larger tumors. Kaplan-Meier curves showed that patients with TDs had worser overall survival (OS) than those without, regardless of TD positions. Patients with TDs in the omentum of greater curvature had the worst prognosis, followed by patients with TDs in the omentum of lesser curvature and patients with no TDs. Tumor deposits in the proximal omentum of greater curvature was an independent prognostic factor for OS. Moreover, only patients classified as pT4 had TDs in the distal omentum of greater curvature. CONCLUSIONS: Patients with TDs in the omentum of greater curvature had the worst prognosis, followed by patients with TDs in the omentum of lesser curvature and patients with no TDs. In addition, partial omentectomy might be practicable for gastric cancer patients classified as T3 or shallower tumors.


Assuntos
Neoplasias Gástricas , Humanos , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Extensão Extranodal/patologia , Prognóstico , Gastrectomia
9.
ACS Appl Mater Interfaces ; 15(1): 1914-1924, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36583973

RESUMO

As an emerging antibacterial strategy, photothermal disinfection attracts increasing attention due to its advantages of high efficacy, wide pertinence, and non-drug resistance. However, the unavoidable shielding of observation by photothermal components and the possible damage to normal tissue caused by hyperthermia restrict its applications. Herein, we propose a composite hydrogel with the ability of on-demand generation of photothermal components and mild-temperature photothermal disinfection by elegantly tuning the binding and release of iodine and starch. The composite hydrogel is obtained by blending iodine-adsorbed pH-responsive ZIF-8 nanoparticles (NPs) with a starch-based hydrogel matrix. Through a convenient pH response, the composite hydrogel leverages the triple functions of iodine, which serves as a disinfectant and reacts with starch to generate a photothermal agent and color indicator, allowing photothermal-chemotherapy combined disinfection on demand. In vitro antibacterial experiments show that the composite hydrogel can respond to the acidification of the microenvironment caused by bacterial metabolism and produce corresponding color changes, realizing naked-eye observation. Meanwhile, under the combined treatment of heating/I2/Zn2+, the composite hydrogel can completely kill Escherichia coli and Staphylococcus aureus at a mild temperature of ∼41 °C. This study represents a breakthrough in on-demand generation of photothermal hydrogels for mild-temperature photothermal disinfection.


Assuntos
Hipertermia Induzida , Iodo , Amido , Hidrogéis/farmacologia , Hidrogéis/química , Iodo/farmacologia , Temperatura , Desinfecção , Fototerapia , Antibacterianos/química
10.
Nat Commun ; 13(1): 7423, 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36456562

RESUMO

Developing dynamic organic ultralong room-temperature phosphorescent (URTP) materials is of practical importance in various applications but remains a challenge due to the difficulty in manipulating aggregate structures. Herein, we report a dish-like molecular architecture via a bottom-up way, featuring guest-responsive dynamic URTP. Through controlling local fragment motions in the molecular architecture, fascinating dynamic URTP performances can be achieved in response to reversible accommodation of various guests, including solvents, alkyl bromides and even carbon dioxide. Large-scale regulations of phosphorescence lifetime (100-fold) and intensity (10-fold) can be realized, presenting a maximum phosphorescence efficiency and lifetime of 78.8% and 483.1 ms, respectively. Moreover, such a dish-like molecular architecture is employed for temperature-dependent multiple information encryption and visual identification of linear alkyl bromides. This work can not only deepen our understanding to construct multifunctional organic aggregates, but also facilitate the design of high-performance dynamic URTP materials and enrich their practical applications.

11.
Acta Biochim Biophys Sin (Shanghai) ; 54(3): 361-369, 2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-35538031

RESUMO

Pancreatic cancer is highly lethal due to its aggressive invasive properties and capacity for metastatic dissemination. Additional therapeutic targets and effective treatment options for patients with tumours of high invasive capacity are required. Ras-related protein-2a (RAP2) is a member of the GTP-binding proteins. RAP2 has been reported to be widely upregulated in many types of cancers via regulating cytoskeleton reorganization, cell proliferation, migration, and adhesion, as well as inflammation. As a member of the RAS oncogene family, which has been demonstrated to drive pancreatic cancer oncogenesis and many other malignancies, the physiological roles of RAP2 in pancreatic cancer have seldom been discussed. In the present study, we explored the correlation between RAP2 expression and the prediction of overall survival of pancreatic cancer patients. Mechanistic studies were carried out to shed light on the role of RAP2 in pancreatic cancer invasion and how RAP2 is regulated in the invasive process. Our results demonstrated that patients with higher RAP2 expression showed unfavourable prognoses. studies demonstrated that silencing of inhibited the invasion of pancreatic cancer cells. Moreover, our results demonstrated that transforming growth factor-ß1 (TGF-ß1), an inducer of the metastatic potential of pancreatic cancer cells, regulates the expression of RAP2 via the transcription factor c-Myc. In conclusion, the present study uncovered RAP2 as a novel predictive marker and therapeutic target for pancreatic cancer.


Assuntos
Neoplasias Pancreáticas , Fator de Crescimento Transformador beta1 , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Humanos , Invasividade Neoplásica , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Regulação para Cima , Proteínas rap de Ligação ao GTP/genética , Proteínas rap de Ligação ao GTP/metabolismo , Neoplasias Pancreáticas
12.
ACS Appl Mater Interfaces ; 14(4): 5856-5866, 2022 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-35061361

RESUMO

Rapid and sensitive diagnostics in the early stage of bacterial infection and immediate treatment play critical roles in the control of infectious diseases. However, it remains challenging to develop integrated systems with both rapid detection of bacterial infection and timely on-demand disinfection ability. Herein, we demonstrate a photonic hydrogel platform integrating visual diagnosis and on-site photothermal disinfection by incorporating Fe3O4@C nanoparticles into a poly(hydroxyethyl methacrylate)-co-polyacrylamide (PHEMA-co-PAAm) matrix. In vitro experiments demonstrate that such a hydrogel can respond to pH variation caused by bacterial metabolism and generate the corresponding color changes to realize naked-eye observation. Meanwhile, its excellent photothermal conversion ability enables it to effectively kill bacteria by destroying cell membranes under near-infrared irradiation. Moreover, the pigskin infection wound model also verifies the bacterial detection performance and disinfection ability of the hydrogel in vivo. Our strategy demonstrates a new approach for visual diagnosis and treatment of bacterial infections.


Assuntos
Desinfetantes/uso terapêutico , Hidrogéis/química , Nanopartículas de Magnetita/uso terapêutico , Infecções Cutâneas Estafilocócicas/diagnóstico por imagem , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Resinas Acrílicas/química , Animais , Desinfetantes/química , Desinfetantes/efeitos da radiação , Escherichia coli/efeitos dos fármacos , Raios Infravermelhos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/efeitos da radiação , Camundongos , Células NIH 3T3 , Terapia Fototérmica , Poli-Hidroxietil Metacrilato/química , Staphylococcus aureus/efeitos dos fármacos , Suínos
13.
Cancers (Basel) ; 13(8)2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33921187

RESUMO

BACKGROUND: Undifferentiated pleomorphic sarcomas (UPS) were one of the most common soft tissue sarcomas. As UPS had relatively high potentials of recurrence and metastasis, we designed two nomograms to better predict the overall survival (OS) and time to recurrence (TTR) for patients who underwent primary surgery. METHODS: The data of UPS patients who underwent primary surgery were extracted from Shanghai Cancer Center, Fudan University. Multivariate analyses were performed using Cox proportional hazards regression to identify independent prognostic factors. Kaplan-Meier analysis was used to compare differences for patients who underwent primary surgery in OS and TTR. Nomograms were designed with the help of R software and validated using calibration curves and receiver operating characteristic curves (ROC). RESULTS: Kaplan-Meier curves showed that patients with older ages (p = 0.0024), deeper locations (p = 0.0422), necrosis (p < 0.0001), G3 French Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC) classification (p < 0.0001), higher Ki-67 (p < 0.0001), higher mitotic index (p < 0.0001), R1/R2 resections (p = 0.0002) and higher invasive depth (p = 0.0099) had shorter OS than the other patients while patients with older ages (p = 0.0108), necrosis (p = 0.0001), G3 FNCLCC classification (p < 0.0001), higher Ki-67 (p = 0.0006), higher mitotic index (p < 0.0001) and R1/R2 resections (p < 0.0001) had shorter TTR compared with those without. Multivariate analyses demonstrated that mitotic rates and surgical margin were independent factors for TTR while age and invasive depth were independent factors for OS. Three parameters were adopted to build the nomograms for 3- and 5-year OS and TTR. The Area Under Curve (AUC) of this nomogram at 3- and 5-year TTR reached 0.802, 0.814, respectively, while OS reached 0.718, 0.802, respectively. Calibration curves for the prediction of 3- and 5-year OS and TTR showed excellent agreement between the predicted and the actual survival outcomes. CONCLUSIONS: Some important parameters could be used to predict the outcome of individual UPS patients such as mitotic age, rates, surgical margin, and invasive depth. We developed two accurate and practicable nomograms that could predict 3- and 5-year OS and TTR for UPS patients, which could be involved in the modern medical decision-making process.

14.
Cancer Manag Res ; 13: 107-115, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33447083

RESUMO

BACKGROUND: The fibrinogen/albumin ratio (FAR) has been widely reported to be a possible biomarker for predicting prognosis in several types of tumors, but the prognostic value of the FAR in pancreatic neuroendocrine neoplasms (Pan-NENs) has not been systematically studied. PATIENTS AND METHODS: In total, 324 patients with Pan-NENs were recruited. The patients were divided into 2 subgroups according to the FAR cutoff value, and clinicopathological characteristics of the 2 subgroups were compared. Overall survival (OS) was the primary endpoint, and progression-free survival (PFS) was the secondary endpoint. The prognostic value of the FAR was analyzed in univariate and multivariate analyses. RESULTS: The optimal cutoff value for the FAR was calculated to be 0.08 for OS. The patients with a FAR ≥0.08 had higher proportions of nonfunctioning tumors, Pan-NECs, grade 3 tumors, and stage IV tumors than those with a FAR <0.08. In the univariate analysis, a FAR ≥ 0.08 was associated with poor OS (hazard ratio (HR) = 2.37, P < 0.001) and PFS (HR = 2.37, P < 0.001). In the multivariate analysis, a FAR ≥0.08 was an independent risk factor for poor OS (HR = 4.70, P < 0.001) and PFS (HR = 1.80, P = 0.006). CONCLUSION: The pretreatment FAR, which includes fibrinogen and albumin, was a feasible and predictive biomarker for prognosis in patients with Pan-NENs. An elevated FAR, based on a cutoff value of 0.08, was an independent risk factor for poor OS and PFS.

15.
Endocrine ; 71(2): 494-501, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32862321

RESUMO

BACKGROUND: Hyperglycaemia has been indicated as a pro-tumoural factor; however, the prognostic role of diabetes mellitus (DM) in pancreatic neuroendocrine tumours (panNETs) remains ambiguous, partly due to the effects of anti-diabetic drugs. We hypothesise that the blood sugar level per se affects the outcome of panNETs, and thus, we investigated the prognostic significance of the fasting blood glucose (FBG) level in resected panNET patients with no pre-existing DM. METHODS: A retrospective cohort study comprising 201 patients with radically resected non-functional panNETs was conducted. A total of 164 patients without pre-existing DM were further studied. An FBG level greater than 5.6 mmol/L was defined as high (otherwise, normal). Survival was evaluated using Kaplan-Meier methods and log-rank tests. Multivariate analyses for survival were performed using the Cox regression model. RESULTS: High FBG levels were significantly associated with poor overall survival (OS; p = 0.019) and recurrence-free survival (RFS; p = 0.011) in resected patients with panNET who had no pre-existing DM. The multivariable-adjusted hazard ratios (HRs) for mortality and recurrence comparing patients with high and normal FBG levels were 12.19 (95% confidence interval (CI) = 1.15-128.78, p = 0.038) and 2.43 (95% CI = 1.03-5.72, p = 0.042), respectively. CONCLUSION: A pre-operative FBG level greater than 5.6 mmol/L is associated with poor OS and RFS metastasis for patients with panNET who undergo radical surgical resection.


Assuntos
Hiperglicemia , Neoplasias Pancreáticas , Glicemia , Jejum , Humanos , Neoplasias Pancreáticas/cirurgia , Prognóstico , Estudos Retrospectivos
16.
Biochim Biophys Acta Rev Cancer ; 1875(2): 188409, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32827580

RESUMO

Carbohydrate antigen 19-9 (CA19-9) is the best validated biomarker and an indicator of aberrant glycosylation in pancreatic cancer. CA19-9 functions as a biomarker, predictor, and promoter in pancreatic cancer. As a biomarker, the sensitivity is approximately 80%, and the major challenges involve false positives in conditions of inflammation and nonpancreatic cancers and false negatives in Lewis-negative Individuals. Lewis antigen status should be determined when using CA19-9 as a biomarker. CA19-9 has screening potential when combined with symptoms and/or risk factors. As a predictor, CA19-9 could be used to assess stage, prognosis, resectability, recurrence, and therapeutic efficacy. Normal baseline levels of CA19-9 are associated with long-term survival. As a promoter, CA19-9 could be used to evaluate the biology of pancreatic cancer. CA19-9 can accelerate pancreatic cancer progression by glycosylating proteins, binding to E-selectin, strengthening angiogenesis, and mediating the immunological response. CA19-9 is an attractive therapeutic target for cancer, and strategies include therapeutic antibodies and vaccines, CA19-9-guided nanoparticles, and inhibition of CA19-9 biosynthesis.


Assuntos
Antígenos Glicosídicos Associados a Tumores/sangue , Biomarcadores Tumorais/sangue , Neoplasias Pancreáticas/patologia , Anticorpos Monoclonais , Progressão da Doença , Glicosilação , Humanos , Estadiamento de Neoplasias , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas
17.
J Hematol Oncol ; 13(1): 130, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33008426

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is a malignancy characterized by a poor prognosis and high mortality rate. Genetic mutations and altered molecular pathways serve as targets in precise therapy. Using next-generation sequencing (NGS), these aberrant alterations can be identified and used to develop strategies that will selectively kill cancerous cells in patients with PDAC. The realization of targeted therapies in patients with PDAC may be summarized by three approaches. First, because oncogenes play a pivotal role in tumorigenesis, inhibition of dysregulated oncogenes is a promising method (Table 3). Numerous researchers are developing strategies to target oncogenes, such as KRAS, NRG1, and NTRK and related molecules, although most of the results are unsatisfactory. Accordingly, emerging strategies are being developed to target these oncogenes, including simultaneously inhibiting multiple molecules or pathways, modification of mutant residues by small molecules, and RNA interference. Second, researchers have attempted to reactivate inactivated tumour suppressors or modulate related molecules. TP53, CDKN2A and SMAD4 are three major tumour suppressors involved in PDAC. Advances have been achieved in clinical and preclinical trials of therapies targeting these three genes, and further investigations are warranted. The TGF-ß-SMAD4 signalling pathway plays a dual role in PDAC tumorigenesis and participates in mediating tumour-stroma crosstalk and modulating the tumour microenvironment (TME); thus, molecular subtyping of pancreatic cancer according to the SMAD4 mutation status may be a promising precision oncology technique. Finally, genes such as KDM6A and BRCA have vital roles in maintaining the structural stability and physiological functions of normal chromosomes and are deficient in some patients with PDAC, thus serving as potential targets for correcting these deficiencies and precisely killing these aberrant tumour cells. Recent clinical trials, such as the POLO (Pancreas Cancer Olaparib Ongoing) trial, have reported encouraging outcomes. In addition to genetic event-guided treatment, immunotherapies such as chimeric antigen receptor T cells (CAR-T), antibody-drug conjugates, and immune checkpoint inhibitors also exhibit the potential to target tumours precisely, although the clinical value of immunotherapies as treatments for PDAC is still limited. In this review, we focus on recent preclinical and clinical advances in therapies targeting aberrant genes and pathways and predict the future trend of precision oncology for PDAC.


Assuntos
Carcinoma Ductal Pancreático/genética , Genes Neoplásicos , Terapia de Alvo Molecular/métodos , Mutação , Neoplasias Pancreáticas/genética , Medicina de Precisão/métodos , Anticorpos Biespecíficos/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Inibidor p16 de Quinase Dependente de Ciclina/antagonistas & inibidores , Reparo do DNA , Receptores ErbB/antagonistas & inibidores , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoconjugados/uso terapêutico , Imunoterapia , Imunoterapia Adotiva , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/fisiologia , Proteínas de Fusão Oncogênica/antagonistas & inibidores , Neoplasias Pancreáticas/terapia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas p21(ras)/antagonistas & inibidores , Proteínas Proto-Oncogênicas p21(ras)/genética , Mutações Sintéticas Letais , Microambiente Tumoral
18.
Cancer Manag Res ; 12: 6727-6737, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32848455

RESUMO

PURPOSE: Pancreatic neuroendocrine tumours (panNETs) are rare tumours of pancreas. Lymphocyte subsets in the peripheral blood are reported to reflect tumour prognosis and progression. The objective of the study is to investigate the hypotheses that the levels of peripheral lymphocytes may reflect tumour progression and may predict the prognosis of pancreatic neuroendocrine tumours (panNETs). PATIENTS AND METHODS: A retrospective cohort study consisting of 73 patients diagnosed with panNETs was conducted. Kaplan-Meier methods and Log rank tests were used to compare the survival rates, and a Cox regression model was used to perform multivariate analyses. RESULTS: panNET patients with distant metastasis were associated with lower peripheral total T cell (p = 0.039) and CD4+ T cell (p = 0.006) counts. Lower peripheral B cells (p = 0.007) and higher peripheral NK cell (p = 0.001) counts indicated worse progression-free survival (PFS) in Log rank tests. In multivariate analyses, low B cell count (hazard ratio (HR): 6.769, 95% confidence interval (CI): 2.158 to 21.228, p = 0.001) and high NK cell count (HR: 3.715, 95% CI: 1.164 to 11.855, p = 0.027) were independent risk factors for progression. NK cells and B cells were also significantly associated with PFS following radical surgical resection. CONCLUSION: Peripheral total T cell and CD4+ T cell counts may reflect the distant metastasis status in panNET patients. The absolute count of peripheral B cells and NK cells may independently predict the progression of panNET patients, making them promising prognostic indicators and potential targets for treatment of panNETs.

19.
Exp Ther Med ; 20(2): 1091-1097, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32742348

RESUMO

Patients with distal (body/tail) pancreatic cancer have been found to present worse outcome than patients with head cancer, which is generally attributed to the great proportion of advanced stages for body/tail cancers upon detection. However, differences in prognosis between head and body/tail pancreatic cancers controlled by stage have not been analyzed in-depth. In this study, differences in prognosis between head and body/tail pancreatic cancers were examined using the Surveillance, Epidemiology, and End Results Program (SEER) (1973-2014 registry, 85,715 cases). We found that patients with body/tail pancreatic cancer had worse prognosis than patients with head cancer for all combined stages [adjusted hazard ratio (HR), 1.03, 95% confidence interval (CI), 1.00-1.05, P=0.025]. Compared with patients with head cancer, patients with body/tail cancer had lower mortality for stage I cancers (HR, 0.85, 95% CI, 0.76-0.94, P=0.001), no difference in mortality for stages II or III (stage II, HR, 1.00, 95% CI, 0.95-1.06, P=0.965; stage III, 0.97, 95% CI, 0.91-1.04, P=0.398), and higher mortality for stage IV (HR, 1.07, 95% CI, 1.04-1.10, P<0.001). In addition, the proportion of body/tail pancreatic cancer increased from 24.9% in 1973 to 36.3% in 2014. Therefore, tumor location of body/tail is an independent adverse prognostic factor for patients with pancreatic cancer. However, this observation is not applicable when controlled by stage (body/tail versus head pancreatic cancer, better stage I, similar stage II/III, and worse stage IV).

20.
Angew Chem Int Ed Engl ; 59(50): 22645-22651, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-32790127

RESUMO

Mechanoluminescence (ML) materials are attracting increasing interest owing to promising applications in various areas. However, to date, it remains a major challenge to develop a precise and universal route to achieving organic ML materials. Herein, we show that ML can be easily realized in organic piezophotonic host-guest crystals, under conditions in which neither the host nor the guest is ML-active. The experimental and theoretical results reveal that excitons of the host generated by piezoelectricity can be harvested effectively by the guest for light emission, owing to the restraint of intersystem crossing process. Moreover, different host-guest crystals are constructed, wherein the emission color, intensity, color purity, and emission duration of ML can be manipulated. This work deepens our understanding of organic ML generation in piezophotonic host-guest crystals and provides an inspiring principle to design more organic ML materials.

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