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1.
Molecules ; 26(6)2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33799909

RESUMO

BACKGROUND: Liver fibrosis, as a common and refractory disease, is challenging to treat due to the lack of effective agents worldwide. Recently, we have developed a novel compound, N-(3,4,5-trichlorophenyl)-2(3-nitrobenzenesulfonamide) benzamide (IMB16-4), which is expected to have good potential effects against liver fibrosis. However, IMB16-4 is water-insoluble and has very low bioavailability. METHODS: Mesoporous silica nanoparticles (MSNs) were selected as drug carriers for the purpose of increasing the dissolution of IMB16-4, as well as improving its oral bioavailability and inhibiting liver fibrosis. The physical states of IMB16-4 and IMB16-4-MSNs were investigated using nitrogen adsorption, thermogravimetric analysis (TGA), HPLC, UV-Vis, X-ray diffraction (XRD) and differential scanning calorimetry (DSC). RESULTS: The results show that MSNs enhanced the dissolution rate of IMB16-4 significantly. IMB16-4-MSNs reduced cytotoxicity at high concentrations of IMB16-4 on human hepatic stellate cells LX-2 cells and improved oral bioavailability up to 530% compared with raw IMB16-4 on Sprague-Dawley (SD) rats. In addition, IMB16-4-MSNs repressed hepatic fibrogenesis by decreasing the expression of hepatic fibrogenic markers, including α-smooth muscle actin (α-SMA), transforming growth factor-beta (TGF-ß1) and matrix metalloproteinase-2 (MMP2) in LX-2 cells. CONCLUSIONS: These results provided powerful information on the use of IMB16-4-MSNs for the treatment of liver fibrosis in the future.

2.
BMC Infect Dis ; 21(1): 299, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33761881

RESUMO

BACKGROUND: COVID-19 patients develop hypolipidemia. However, it is unknown whether lipid levels have improved and there are potential sequlae in recovered patients. OBJECTIVE: In this follow-up study, we evaluated serum lipidemia and various physiopathological laboratory values in recovered patients. METHODS: A 3-6 month follow-up study was performed between June 15 and September 3, 2020, to examine serum levels of laboratory values in 107 discharged COVID-19 patients (mild = 59; severe/critical = 48; diagnoses on admission). Sixty-one patients had a revisit chest CT scan. A Wilcoxon signed-rank test was used to analyze changes in laboratory values at admission and follow-up. RESULTS: LDL-c and HDL-c levels were significantly higher at follow-up than at admission in severe/critical cases (p <  0.05). LDL-c levels were significantly higher at follow-up than at admission in mild cases (p <  0.05). Coagulation and liver functional values were significantly improved at follow-up than at admission for patients (p <  0.05). Increases in HDL-c significantly correlated with increases in numbers of white blood cells (p <  0.001) during patients' recovery. With exclusion of the subjects taking traditional Chinese medicines or cholesterol-lowering drugs, LDL-c and HDL-c levels were significantly increased at follow-up than at admission in severe/critical cases (p <  0.05). Residue lesions were observed in CT images in 72% (44 of 61) of follow-up patients. CONCLUSIONS: Improvements of LDL-c, HDL-c, liver functions, and incomplete resolution of lung lesions were observed at 3-6 month follow-up for recovered patients, indicating that a long-term recovery process could be required and the development of sequelae such as pulmonary fibrosis could be expected in some patients.


Assuntos
/sangue , Colesterol/sangue , Idoso , Progressão da Doença , Dislipidemias , Feminino , Seguimentos , Hospitalização , Humanos , Fígado , Masculino , Pessoa de Meia-Idade
3.
Clin Cancer Res ; 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33558426

RESUMO

PURPOSE: Fluzoparib (PARP inhibitor) showed promising antitumor activity for advanced ovarian cancer in a phase I study. This study aimed to assess the efficacy and safety of fluzoparib in patients with germline BRCA1/2-mutated recurrent ovarian cancer. PATIENTS AND METHODS: This open-label, multicenter, single-arm, phase II study enrolled patients with platinum-sensitive recurrent ovarian cancer and germline BRCA1/2 mutation who had previously received two to four lines of platinum-based chemotherapy. Fluzoparib 150 mg was administered orally twice daily. The primary endpoint was independent review committee (IRC)-assessed objective response rate per RECIST v1.1. RESULTS: A total of 113 patients were enrolled and received at least one dose of fluzoparib. As of data cutoff on March 21, 2020, the median follow-up period was 15.9 months (interquartile range, 13.5-18.5). The IRC- and investigator-assessed objective response rates were 69.9% [95% confidence interval (CI), 60.6-78.2] and 70.8% (95% CI, 61.5-79.0), respectively. The objective response rates were similar across all prespecified subgroups. The median IRC- and investigator-assessed progression-free survival was 12.0 months (95% CI, 9.3-13.9) and 10.3 months (95% CI, 9.2-12.0), respectively. The 12-month survival rate was 93.7% (95% CI, 87.2-96.9). Grade ≥3 adverse events occurred in 63.7% (72/113) of the patients, with the most common one being anemia/decreased hemoglobin. Adverse events that led to treatment interruption, dose reduction, and discontinuation occurred in 39.8%, 34.5%, and 0.9% of patients, respectively. One treatment-related death occurred. CONCLUSIONS: Fluzoparib demonstrated promising antitumor activity and acceptable safety profile in germline BRCA1/2-mutated, platinum-sensitive relapsed ovarian cancer. Thus, fluzoparib might be a novel treatment option for this population.

4.
Clin Appl Thromb Hemost ; 27: 1076029620975484, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33591842

RESUMO

Venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT) occurs more frequently in cancer patients than in the general population. A retrospective cross-sectional study was carried out in patients with solid tumor complicated with VTE admitted to the Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between January 1st, 2008 and December 31th, 2017. The incidence of VTE in hospitalized cancer patients was 1.8%, twice the incidence of VTE in hospitalized non-cancer patients. The annual incidence of cancer-associated VTE in our center varied between 1.6% in 2015 and 0.4% in 2009 with an overall average incidence of 1.3% over the research decade. BMI values of 549(67.7%) cancer patients were within the normal range, but none of patients had BMI greater than 35 kg/m2. 747(92.1%) cancer patients had ECOG PS score ≤ 2 and 481(59.3%) had distant metastasis. Patients with pancreatic, bladder, ovarian and endometrial cancer had the highest incidence of VTE. Upper extremity DVT (47.2%) was more common in cancer patients and might be closely associated with CVC (74.9%), while lower extremities DVT (36.1%) intended to PE development (15.0%). The annual incidence rates showed a fluctuating and upward trend over the research decade. VTE occurrence was closely related to tumor stage, tumor site, catheterization and anti-neoplasm therapy in cancer patients.

5.
Mol Nutr Food Res ; 65(6): e2000780, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33560577

RESUMO

SCOPE: Although pickled radish is widely consumed worldwide, few studies have investigated the nutritional benefits of bioactive compounds extracted from pickled radish. In this study, the authors investigate the relationship among dietary phenolic compounds, lipid accumulation, and gut microbiota. METHOD AND RESULTS: Three phenolic compounds 2,6-dihydroxyacetophenone (DHAP), 4-hydroxyphenethyl alcohol (4-HPEA), and 4-hydroxybenzaldehyde (HBA) are extracted from pickled radish. LO2 cells treated with free fatty acid are first used to explore the impact of the above three compounds at different doses on reducing lipid levels. The effects of the three compounds on obesity and the gut microbiota are further investigated in high-fat diet (HFD)-induced KM mice. Results show that three compounds inhibited the lipid accumulation in LO2 cells. The results of animal experiments reveal that three compounds prevented body weight gain and significantly decreased serum lipid levels. Treatment with DHAP, HPEA, and HBA reversed gut microbiome dysbiosis in HFD-induced mice. The three phenolic compounds increase Odoribacter, and decrease Helicobacter and Mucispirillum. Notably, DHAP and HBA reduce the HFD-induced increase in the Firmicutes/Bacteroidetes ratio. CONCLUSION: These data suggest that phenolic compounds extracted from pickled radish possess excellent lipid-lowering capacity, providing a theoretical basis for further analysis of the nutritional value of pickled radish.

6.
J Ovarian Res ; 14(1): 12, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33423683

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of PLD in treating of in patients who experience epithelial ovarian, fallopian tubal, and peritoneal cancer progression within 12 months after the first-line platinum-based therapy. METHODS: This was an open-label, single-arm and multicenter clinical trial. The ORR was the interim primary objective, and the DCR, AEs and QOL were the secondary objectives. The impact of factors on efficacy outcomes, the change trend of CA125 and the artificial platinum-free interval were exploratory endpoints. RESULTS: Totally, 115 patients were enrolled in this study and included in the ITT population. Moreover, 101 patients were included in the safety population. The median follow-up time was 4 months (IQR 2-6). In the ITT population, the confirmed ORR was 37.4% (95% CI, 28.4-46.4%), and the DCR was 65.2% (95% CI, 56.4-74.1%). The previous response status to platinum-based chemotherapy and baseline CA125 levels were significantly correlated with the ORR. The ORR was significantly higher in patients with a CA125 decrease after the first cycle than in the patients with a CA125 increase. The most common grade 3 or higher AE was hand-foot syndrome (3 [3.0%] of 101 patients). No statistically significant differences existed between the baseline and the postbaseline questionnaires. CONCLUSIONS: For patients who experience platinum-resistant and platinum-refractory relapse, the use of PLD may be acceptable because of the associated satisfactory efficacy, low frequency of AEs and high patient QOL. Moreover, a low CA125 level at baseline and a reduction in CA125 after the first cycle are predictive factors for satisfactory efficacy.

7.
J Agric Food Chem ; 69(5): 1647-1655, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33497204

RESUMO

Reactive oxygen species (ROS) are single-electron-bearing oxidation-reduction products that are mainly produced in mitochondria. Excessive ROS accumulation may lead to oxidative damage. Docosahexaenoic acid (DHA) is an essential component of brain phospholipids and is mainly derived from the diet. Its antioxidant activities have been extensively studied. However, its regulatory roles in mitochondria and the underlying mechanism remain to be elucidated. In this study, the DHA's effect on cellular antioxidant capacity and mitochondrial functions was examined in HepG2 cells. The results showed that 100 µM DHA decreased cellular and mitochondrial ROS levels to 75.2 ± 9.4% (P < 0.05) and 55.1 ± 1.4% (P < 0.01), respectively. It also increased the total antioxidant capacity by 55.6 ± 0.1 and 49.2 ± 1.1% (P < 0.05), based on ABTS and FRAP assay results, respectively. Consistently, it increased the activities and gene expression of major antioxidant enzymes by at least 35 and 40% (P < 0.05), respectively. Furthermore, DHA promoted mitochondrial functions and biogenesis. These data suggested that DHA's antioxidant activity can be attributed to its enhancement of mitochondrial functions and biogenesis. This study may shed light on the molecular mechanisms underlying DHA's function in improving resistance to and relieving the symptoms of chronic disease.

8.
Sci Total Environ ; 753: 141949, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-32891999

RESUMO

Bisphenol S (BPS) is the major substitute for the production of bisphenol A (BPA)-free products and detected in both food and environment. Although the relationship between BPA exposure and increased risk of obesity and diabetes has been noted, the potential influence of BPS is not fully understood. Herein, a non-targeted lipidomic study was performed to explore BPA/BPS exposure actions using the 3T3-L1 preadipocyte differentiation model, and revealed the comprehensive lipidome disturbance induced by either BPA or BPS exposure at different doses of 0.01, 1 and 100 µM. BPA was more potent than BPS in disturbance of lipid metabolism. A considerable similarity of BPS exposure to BPA was discovered. The key lipid remodeling in response to exposure was found to involve the cardiolipins, phosphatidylglycerols and fatty acids metabolic pathways, providing novel clues of potential mechanism in which both BPA and BPS exposure could be associated with increased risk of insulin resistance. Our study supplies the perspective into the lipidome response to environmental stress induced by BPA/BPS, and shows that BPA-free products are not necessarily safer. Substitution of BPA by its structural analog BPS should be therefore performed with caution.


Assuntos
Compostos Benzidrílicos , Lipidômica , Animais , Compostos Benzidrílicos/toxicidade , Camundongos , Fenóis/toxicidade , Sulfonas
9.
Cancer Manag Res ; 12: 12021-12028, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33262652

RESUMO

Background: Coronavirus disease 2019 (COVID-19) is an infectious disease that has been spreading very fast worldwide. Up to now, there is scarce information regarding the clinical features and short-term outcomes of infected patients with cancer. Methods: We performed a retrospective study in Wuhan Union Hospital from Feb 14, 2020, to Mar 15, 2020, China. Data were retrieved including demographic and clinical features, laboratory findings, and outcome data. Patients were classified into the discharged group and undischarged group by the 4-week outcomes from admission. Difference analysis and correlation analysis were performed between the two groups. Results: A total of 37 patients were enrolled in the study, including 27 cancer survivors in routine follow-up. Breast cancer (18.9%) was the most frequent cancer type, and common symptoms included cough (54.1%), fever (48.6%), and fatigue (27%). Lymphocytopenia and hypoproteinemia were much frequent in patients who had received chemotherapy, radiotherapy, or surgery within the past month. However, the concentration of D-dimer (median: 3.75 vs 0.43, P =0.010) and fibrin degradation products (median: 23.60 vs 1.80, P =0.002) were evidently increased in this population compared with cancer survivors. At the end of follow-up, 83.8% of the enrolled patients were discharged. Among the discharged, women (48.6%) and cancer survivors (67.6%) showed better short-term outcomes. The elevated level of FDP was significantly higher in the undischarged group (median: 21.85 vs 2.00, P =0.049). The proportion of CD3-positive lymphocyte cells and CD4-positive lymphocytes was correlated with short-term outcomes. Conclusion: Peripheral lymphocyte subset (CD3-positive and CD4-positive) on admission as a novel biomarker had a potential association with early efficacy. Cancer survivors in routine follow-up would achieve better short-term outcomes. COVID-19 patients with cancer should gain more attention and close monitoring.

10.
J Appl Microbiol ; 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33275816

RESUMO

AIMS: To search for a set of reference genes for reliable gene expression analysis in the globally important marine coccolithophore Emiliania huxleyi -virus model system. METHODS AND RESULTS: Fifteen housekeeping genes (CDKA, CYP15, EFG3, POLAI, RPL30, RPL13, SAMS, COX1, GPB1-2, HSP90, TUA, TUB, UBA1, CAM3 and GAPDH) were evaluated for their stability as potential reference genes for qRT-PCR using ΔCt, geNorm, NormFinder, Bestkeeper and RefFinder software. CDKA, TUA and TUB genes were tested as loading controls for Western blot in the same sample panel. Additionally, target genes associated with cell apoptosis, i.e., metacaspase genes, were applied to validate the selection of reference genes. The analysis results demonstrated that putative housekeeping genes exhibited significant variations in both mRNA and protein content during virus infection. After a comprehensive analysis with all of the algorithms, CDKA and GAPDH were recommended as the most stable reference genes for E huxleyi virus (EhV) infection treatments. For Western blot, significant variation was seen for TUA and TUB, while CDKA was stably expressed, consistent with the results of qRT-PCR. CONCLUSIONS: CDKA and GAPDH are the best choice for gene and protein expression analysis than the other candidate reference genes under EhV infection conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: The stable internal control genes identified in this work will help to improve the accuracy and reliability of gene expression analysis and gain insight into complex E. huxleyi-EhV interaction regulatory networks.

11.
Biomed Res Int ; 2020: 8882576, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33224983

RESUMO

Background: In the past few years, the immune system and tumor immune microenvironment are becoming increasingly popular as more work has been accomplished in this field. However, nomograms based on immune-related characteristics for prognosis prediction of cervical cancer have not been fully explored to our knowledge. We constructed a novel immune score-based nomogram to predict patients with high risk and poor prognosis. Materials and Methods: 198 patients with cervical cancer from The Cancer Genome Atlas (TCGA) database were included in our study. Immune scores were generated with Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm, and clinic-pathological characteristics were also included for subsequent analysis. Cox proportional hazards regression models were performed for univariate and multivariate analyses to screen the significant factors, and a prognostic nomogram was built. Bootstrap resampling analysis was used for internal validation. The calibration curve and concordance index (C-index) were used to assess the predictive performance of the nomogram. Results: Patients were split into three subgroups based on immune scores. We found that patients with high immune scores conferred significantly better overall survival (OS) compared with those with medium and low immune scores (hazard ratio (HR), 0.305; 95% confidence interval (CI), 0.108-0.869). A nomogram with a C-index of 0.720 had a favorable performance for predicting survival rate for clinical use by combining immune scores with other clinical features. The calibration curves at 3 and 5 years suggested a good consistency between the predicted OS and the actual OS probability. Conclusions: Our work highlights the potential clinical application significance of immune score-based nomogram in predicting the OS of cervical cancer patients.

12.
J Nanobiotechnology ; 18(1): 161, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33160373

RESUMO

BACKGROUND: Most cancers favor glycolytic-based glucose metabolism. Hexokinase-2 (HK2), the first glycolytic rate-limiting enzyme, shows limited expression in normal adult tissues but is overexpressed in many tumor tissues, including ovarian cancer. HK2 has been shown to be correlated with the progression and chemoresistance of ovarian cancer and could be a therapeutic target. However, the systemic toxicity of HK2 inhibitors has limited their clinical use. Since follicle-stimulating hormone (FSH) receptor (FSHR) is overexpressed in ovarian cancer but not in nonovarian healthy tissues, we designed FSHR-mediated nanocarriers for HK2 shRNA delivery to increase tumor specificity and decrease toxicity. RESULTS: HK2 shRNA was encapsulated in a polyethylene glycol-polyethylenimine copolymer modified with the FSH ß 33-53 or retro-inverso FSH ß 33-53 peptide. The nanoparticle complex with FSH peptides modification effectively depleted HK2 expression and facilitated a shift towards oxidative glucose metabolism, with evidence of increased oxygen consumption rates, decreased extracellular acidification rates, and decreased extracellular lactate and glucose consumption in A2780 ovarian cancer cells and cisplatin-resistant A2780CP counterpart cells. Consequently, cell proliferation, invasion and migration were significantly inhibited, and tumor growth was suppressed even in cisplatin-resistant ovarian cancer. No obvious systemic toxicity was observed in mice. Moreover, the nanoparticle complex modified with retro-inverso FSH peptides exhibited the strongest antitumor effects and effectively improved cisplatin sensitivity by regulating cisplatin transport proteins and increasing apoptosis through the mitochondrial pathway. CONCLUSIONS: These results established HK2 as an effective therapeutic target even for cisplatin-resistant ovarian cancer and suggested a promising targeted therapeutic approach.

13.
J Exp Clin Cancer Res ; 39(1): 183, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32907622

RESUMO

BACKGROUND: NEK2, a serine/threonine kinase involved in mitosis, has been found to function in chromosome instability, tumor progression and metastasis, but its role in cervical cancer radioresistance remains unknown. METHODS: We detected the protein levels of NEK2 in cervical carcinoma tissues and paired paracarcinoma tissues by immunohistochemistry. The roles of NEK2 in oncogenesis were examined using cell growth and colony formation assays, EdU assay, apoptosis assay as well as in vivo mouse model. γ-H2AX and Rad51 foci formation, neutral comet assay and clonogenic cell survival assay were applied to determine the radiosensitivity of cervical cancer cells. RNA-seq was performed to identify the downstream effector of NEK2. The gene expression levels were measured by Real-time PCR. RESULTS: We report that NEK2 protein level is overexpressed and correlated with the tumor stage and lymph node metastasis in cervical cancer tissues. Furthermore, we provided evidence that depletion of NEK2 impairs oncogenesis and enhances radiosensitivity in cervical cancer. Using RNA sequencing, we identify Wnt1 as a key downstream effector of NEK2. Knockdown of NEK2 downregulates the mRNA and protein levels of Wnt1, thereby inhibiting the activation of the Wnt/ß-catenin signaling pathway. More importantly, the observed consequences induced by NEK2 depletion in cervical cancer cells can be partially rescued by Wnt1 overexpression. CONCLUSIONS: Our results demonstrate that NEK2 activates the Wnt/ß-catenin signaling pathway via Wnt1 to drive oncogenesis and radioresistance in cervical cancer, indicating that NEK2 may be a promising target for the radiosensitization of cervical cancer.

14.
Brachytherapy ; 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32893146

RESUMO

PURPOSE: COVID-19 broke out in late 2019 and rapidly spread around the world and became a pandemic. This highly contagious disease affects routine health care services and patients with cancer who are susceptible to it. Delivering brachytherapy on time is critical for patients with cancer to get better prognosis. The purpose of this study is to present workflow and standard for radiation centers to deliver brachytherapy and avoid cross-infection during the COVID-19 pandemic. METHODS AND MATERIALS: This study combined previous literature and guidelines of precaution with clinical experience in the COVID-19 pandemic. RESULTS: A workflow covering patients' screening, health care workers' precaution, training, and other aspects of the whole brachytherapy procedure was established. CONCLUSIONS: From the reopening of radiation center to mid-May in 2020, there is no hospital infection of COVID-19 in patients or health care workers. This recommendation is effective and helpful to other cancer centers.

15.
Oncol Lett ; 20(3): 2387-2395, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32782556

RESUMO

p21-activated kinase 6 (PAK6), a member of the serine/threonine kinase family, has been reported to be involved in numerous types of cancers. The present study aimed to investigate the role of PAK6 in cervical cancer. In the present study, PAK6 expression was evaluated in tissue microarrays and cell lines by using immunohistochemistry and western blotting. The mRNA level of PAK6 was evaluated by reverse transcription quantitative PCR. The Wnt/ß-catenin signaling-related protein expression was detected by western blotting following short hairpin (sh)RNA-mediated PAK6 knockdown or PAK6 overexpression. Cell proliferation was determined using Cell Countink Kit-8. Migration, invasion and colony formation were further assessed following PAK6 knockdown or overexpression. Co-immunoprecipitation (Co-IP) and fluorescence colocalization microscopy were used to detect the interaction between PAK6 and GSK3ß. The results from tissue microarray revealed that the expression levels of PAK6 in cervical cancer tissues were upregulated. The downregulation of PAK6 expression levels using shRNA not only decreased cell growth and proliferation, but it also inhibited the migration and invasion of HeLa cells. Conversely, the overexpression of PAK6 promoted the proliferation, migration and invasion of HeLa cells. In addition, the expression levels of proteins involved in the Wnt/ß-catenin signaling pathway were modified in the PAK6 knockdown group, including downregulation of GSK3ß phosphorylation and Cyclin D1 protein, and upregulation of ß-catenin phosphorylation and E-cadherin. In contrast, following the overexpression of PAK6, the Wnt/ß-catenin signaling pathway was activated. Further investigation using fluorescence microscopy and Co-IP assays indicated that PAK6 may interact with GSK3ß. In conclusion, the findings of the present study suggested that PAK6 may serve a role in promoting cervical cancer through activating the Wnt/ß-catenin signaling pathway.

16.
Micromachines (Basel) ; 11(7)2020 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32674334

RESUMO

Three-dimensional (3D) bioprinting is a novel technology utilizing biocompatible materials, cells, drugs, etc. as basic microcomponents to form 3D artificial structures and is believed as a promising method for regenerative medicine. Droplet-based bioprinting can precisely generate microspheres and manipulate them into organized structures with high fidelity. Biocompatible hydrogels are usually used as bioinks in 3D bioprinting, however, the viscosity of the bioink could be increased due to the additives such as cells, drugs, nutrient factors and other functional polymers in some particular applications, making it difficult to form monodispersed microspheres from high-viscosity bioink at the orifice of the nozzle. In this work, we reported a novel microfluidic-based printing nozzle to prepare monodispersed microspheres from high-viscosity bioink using the phase-inversion method. Different flowing conditions can be achieved by changing the flow rates of the fluids to form monodispersed solid and hollow microspheres using the same nozzle. The diameter of the microspheres can be tuned by changing the flow rate ratio and the size distribution of the microspheres is narrow. The prepared calcium alginate microspheres could also act as micro-carriers in drug delivery.

17.
Lancet Oncol ; 21(7): 904-913, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32479787

RESUMO

BACKGROUND: Patients with cancer are a high-risk population in the COVID-19 pandemic. We aimed to describe clinical characteristics and outcomes of patients with cancer and COVID-19, and examined risk factors for mortality in this population. METHODS: We did a retrospective, multicentre, cohort study of 205 patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and with a pathological diagnosis of a malignant tumour in nine hospitals within Hubei, China, from Jan 13 to March 18, 2020. All patients were either discharged from hospitals or had died by April 20, 2020. Clinical characteristics, laboratory data, and cancer histories were compared between survivors and non-survivors by use of χ2 test. Risk factors for mortality were identified by univariable and multivariable logistic regression models. FINDINGS: Between Jan 13 and Mar 18, 2020, 205 patients with cancer and laboratory-confirmed SARS-CoV-2 infection were enrolled (median age 63 years [IQR 56-70; range 14-96]; 109 [53%] women). 183 (89%) had solid tumours and 22 (11%) had haematological malignancies. The median duration of follow-up was 68 days (IQR 59-78). The most common solid tumour types were breast (40 [20%] patients), colorectal (28 [14%]), and lung cancer (24 [12%]). 54 (30%) of 182 patients received antitumour therapies within 4 weeks before symptom onset. 30 (15%) of 205 patients were transferred to an intensive care unit and 40 (20%) died during hospital admission. Patients with haematological malignancies had poorer prognoses than did those with solid tumours: nine (41%) of 22 patients with haematological malignancies died versus 31 (17%) of 183 patients with solid tumours (hazard ratio for death 3·28 [95% CI 1·56-6·91]; log rank p=0·0009). Multivariable regression analysis showed that receiving chemotherapy within 4 weeks before symptom onset (odds ratio [OR] 3·51 [95% CI 1·16-10·59]; p=0·026) and male sex (OR 3·86 [95% CI 1·57-9·50]; p=0·0033) were risk factors for death during admission to hospital. INTERPRETATION: Patients with cancer and COVID-19 who were admitted to hospital had a high case-fatality rate. Unfavourable prognostic factors, including receiving chemotherapy within 4 weeks before symptom onset and male sex, might help clinicians to identify patients at high risk of fatal outcomes. FUNDING: National Natural Science Foundation of China.


Assuntos
Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/patologia , Neoplasias/mortalidade , Neoplasias/patologia , Pneumonia Viral/mortalidade , Pneumonia Viral/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , China/epidemiologia , Infecções por Coronavirus/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Pandemias , Pneumonia Viral/terapia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
19.
Cancer Discov ; 10(6): 783-791, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32345594

RESUMO

The novel COVID-19 outbreak has affected more than 200 countries and territories as of March 2020. Given that patients with cancer are generally more vulnerable to infections, systematic analysis of diverse cohorts of patients with cancer affected by COVID-19 is needed. We performed a multicenter study including 105 patients with cancer and 536 age-matched noncancer patients confirmed with COVID-19. Our results showed COVID-19 patients with cancer had higher risks in all severe outcomes. Patients with hematologic cancer, lung cancer, or with metastatic cancer (stage IV) had the highest frequency of severe events. Patients with nonmetastatic cancer experienced similar frequencies of severe conditions to those observed in patients without cancer. Patients who received surgery had higher risks of having severe events, whereas patients who underwent only radiotherapy did not demonstrate significant differences in severe events when compared with patients without cancer. These findings indicate that patients with cancer appear more vulnerable to SARS-CoV-2 outbreak. SIGNIFICANCE: Because this is the first large cohort study on this topic, our report will provide much-needed information that will benefit patients with cancer globally. As such, we believe it is extremely important that our study be disseminated widely to alert clinicians and patients.This article is highlighted in the In This Issue feature, p. 747.


Assuntos
Betacoronavirus , Infecções por Coronavirus/terapia , Neoplasias , Pneumonia Viral/terapia , Idoso , China/epidemiologia , Estudos de Coortes , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Surtos de Doenças , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/patologia , Neoplasias/terapia , Neoplasias/virologia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Respiração Artificial
20.
Oncologist ; 25(4): e659-e667, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32297441

RESUMO

BACKGROUND: The objective of this study was to develop and validate a nomogram to predict 1-year overall survival (OS) and 2-year OS in patients with high-grade digestive neuroendocrine neoplasms (NENs) as well as to guide selection of subgroups that could benefit from systemic chemotherapy. SUBJECTS, MATERIALS, AND METHODS: We performed a retrospective analysis of 223 patients with NENs of the gut and hepato-biliary-pancreatic system from four centers included in the development cohort. The nomogram was externally validated in a cohort of 90 patients from another one. RESULTS: The final model included lactate dehydrogenase, performance status, stage, Ki67, and site of primary tumor, all of which had a significant effect on OS. The uncorrected C-index was 0.761 for OS, and the bias-corrected C-index was 0.744. Predictions correlated well with observed 1-year and 2-year outcomes (judged by eye). The area under the time-dependent receiver operating characteristic curve at 12 months and 24 months was 0.876 and 0.838, respectively. The nomogram performed well in terms of both discrimination and calibration when applied to the validation cohort, and OS was significantly different between the two groups classified by nomogram score (log-rank p < .001). CONCLUSION: The validated nomogram provided useful prediction of OS, which can be offered for clinicians to improve their abilities to assess patient prognosis, to create clinical risk groups for informing treatment or for patient stratification by disease severity in clinical trials. IMPLICATIONS FOR PRACTICE: The high-grade neuroendocrine neoplasms of the digestive system are rare malignancies with great heterogeneity. An overall survival nomogram was developed and externally validated in this study. Two subgroups were classified by the nomogram score, and platinum-based chemotherapy may not bring clinical benefit for the low-risk patients.

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