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We aimed to identify risk factors for early hypocalcemia after parathyroidectomy in patients with secondary hyperparathyroidism. We retrospectively enrolled 106 of 120 consecutive patients with secondary hyperparathyroidism who underwent parathyroidectomy between January 2019 and July 2021. Perioperative laboratory parameters, preoperative computerized tomography (CT) images, and postoperative histology were evaluated. Parathyroid calcification was defined as hyperdense regions with a density of > 130 Hounsfield Units on CT images of the parathyroid. Subtotal parathyroidectomy, total parathyroidectomy without auto-transplantation, or total parathyroidectomy with auto-transplantation were performed in the present study. Postoperative hypocalcemia was defined as a serum calcium concentration < 2.1 mmol/L within 4 days of surgery. The participants were categorized according to the presence (n = 33) or absence (n = 73) of postoperative hypocalcemia. The demographics, comorbidities, and surgical details were similar in the two groups. Multivariate analysis showed that the preoperative alkaline phosphatase activity, serum intact parathyroid hormone and calcium concentrations, and parathyroid calcification were independent risk factors for postoperative hypocalcemia (all P < 0.05). Receiver operating characteristic analysis generated areas under the curves for preoperative alkaline phosphatase, intact parathyroid hormone, and parathyroid calcification of 0.82, 0.80, and 0.70, respectively (all P < 0.05). Cut-off values for preoperative alkaline phosphatase (> 242.9 IU/L) and intact parathyroid hormone (> 2,104 pg/mL) were found to be predictive of postoperative hypocalcemia. High preoperative alkaline phosphatase activity and serum intact parathyroid hormone concentration and low serum calcium are associated with higher risks of postoperative hypocalcemia. Calcification of the parathyroid may represent a novel radiologic means of predicting postoperative hypocalcemia.
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Hiperparatireoidismo Secundário , Hipocalcemia , Humanos , Paratireoidectomia/métodos , Hipocalcemia/etiologia , Cálcio , Fosfatase Alcalina , Estudos Retrospectivos , Diálise Renal/efeitos adversos , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/cirurgia , Hormônio Paratireóideo , Fatores de RiscoRESUMO
BACKGROUND: There occurs huge heterogeneity in clinical outcomes for patients with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs). The purpose of this study was to indicate genetic biomarkers predicting primary resistance of EGFR-TKIs in these patients. PATIENTS AND METHODS: Using a next-generation sequencing panel with 168 cancer-related genes, matched tumor biopsy and plasma samples before treatments from patients with NSCLC were analyzed. Patients taking EGFR-TKIs were followed-up with imaging examination. Correlation of co-alterative genes with progression-free survival (PFS) was analyzed. RESULTS: Of the 48 patients treated with EGFR-TKIs, 46 (95.83%) had at least 1 genetic co-variant beyond EGFR mutation. Multivariate analysis indicated that RB1, PIK3CA, and ERBB2 co-alterations, rather than number of co-alterative genes, were independently associated with poorer PFS. Grouping patients by specific gene status showed best likelihood ratio χ2, Akaike information criterion, and Harrell concordance index. The median PFS for patients in group A (less genetic co-variations and wild specific genes), group B (more genetic co-variations and wild specific genes), group C (less genetic co-variations and altered specific genes), and group D (more genetic co-variations and altered specific genes) were 10.4, 9.13 (vs. group A; P = .3112), 6.33 (vs. group B; P = .0465), and 3.90 (vs. group C; P = .0309) months, respectively. CONCLUSIONS: This study revealed a high concomitant genetic alteration rate in patients with EGFR-mutated NSCLC. Specific gene variants were more important than number of altered genes in predicting poor PFS, and may help select patients needing new treatment strategies.
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Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Taxa de SobrevidaRESUMO
Solvothermal reaction of zinc meso-tetra(4-carboxyphenyl)porphyrin and 2,6-diaminopurine with zinc salt in DMF affords a three-dimensional bioMOF (1-α). Its infinite rod-shaped building block features an alternation of octahedral Zn4O and paddle-wheel Zn2 clusters bridged by 2,6-diaminopurines. The paddle-wheel Zn2 cluster undergoes reversible transformation with half into quasi-paddle-wheel Zn2 cluster and the other half into two tetrahedral mononuclear clusters upon release/uptake of guest molecules, resulting in a new phase 1-ß. This single-crystal to single-crystal transformation is accompanied by luminescence on/off switching, possibly associated with the structural conversion between the porphyrin-ligand-based photoactive 1-α and the porphyrin-stacking-caused non-photoactive 1-ß. Interestingly, 1-ß exhibits quick luminescence turn-on in alcohol vapor instead of other volatile organic solvents by transforming into an intermediate phase 1-γ, which shows a partial luminescence enhancing likely due to the intermittent porphyrin π-π stacking. In view of experimental results and theoretical calculations, this distinctive alcohol-vapor-induced luminescence turn-on is attributed to the coordination ability to porphyrin-bound zinc ion, molecular size, and vapor pressure, in which methanol and ethanol are particularly favored.
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An anionic microporous metal-organic framework (1), featuring a combination of mononuclear and tetranuclear zinc clusters and a mix-and-match strategy of two different types of organic ligands, has been successfully constructed via a solvothermal reaction. Its luminescence can be exclusively quenched by acetone. In situ single-crystal X-ray diffraction studies reveal the specific acetone binding sites and the existence of multiple hydrogen bonds between acetone and the framework. Together with its chemical and thermal stability, 1 has been demonstrated to be a potential luminescence probe for the rapid detection of acetone with a remarkable anti-interference and a low detection limit (1.85 ppm).
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Porous materials that can undergo pore-structure adjustment to better accommodate specific molecules are ideal for separation and purification. Here, we report a stable microporous metal-organic framework, JNU-1, featuring one-dimensional diamond-shaped channels with a high density of open metal sites arranged on the surface for the cooperative binding of acetylene. Together with its framework flexibility and appropriate pore geometry, JNU-1 exhibits an induced-fit behavior for acetylene. The specific binding sites and continuous framework adaptation upon increased acetylene pressure are validated by molecular modeling and inâ situ X-ray diffraction study. This unique induced-fit behavior endows JNU-1 with an unprecedented increase in the acetylene binding affinity (adsorption enthalpy: up to 47.6â kJ mol-1 at ca. 2.0â mmol g-1 loading).
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The present study aims to investigate the effect of miR-30a on the proliferative and invasive abilities of breast cancer cells, and to observe the role of miR-30a in the pathogenesis of breast cancer. With the increase of pathological grade and malignant degree of breast cancer cells, the miR-30a expression level gradually decreased (P<0.01). Transfection with miR-30a mimic significantly inhibited the proliferative and invasive ability of SK-BR-3 cells (P<0.01), while transfection with anti-miR-30a significantly improved the proliferative and invasive ability of these cells (P<0.01). It was revealed using bioinformatic methods that Snail was the functional target gene of miR-30a, and this was verified by the results of a luciferase reporter gene assay. The results of analysis of Snail expression in breast cancer tissues and breast cancer cells revealed that with the increase in pathological grade and malignant degree of breast cancer cells, Snail expression levels gradually increased (P<0.01). Western blotting revealed that miR-30a significantly inhibited Snail expression in SK-BR-3 cells, upregulated the expression of EMT-associated E-cadherin, and downregulated the expression of EMT-associated N-cadherin and Vimentin. MiR-30a was able to affect the proliferation and invasion of breast cancer cells by regulating Snail expression, and therefore has a regulatory effect on the occurrence and development of breast cancer.
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Some studies investigated the association between highly up-regulated in liver cancer (HULC) and the overall survival (OS) of cancer. However, the results were conflicted and inconclusive. Therefore, we performed this meta-analysis to determine the association between HULC and the OS of cancer. A comprehensive online search was conducted on Online electronic databases (PubMed, EMBASE, and Wanfang database) from the earliest date to Aug 30, 2016. The strength of the association was calculated with the HRs and respective 95% CIs. The expression of HULC was significantly associated with OS of cancers (HR = 2.12; 95% CI 1.61 - 2.79; P<0.00001). In the subgroup analysis by ethnicity, the expression of HULC was significantly associated with OS in Chinese patients (HR = 2.04; 95% CI 1.55 - 2.70; P<0.00001). In the subgroup analysis by cancer type, HULC was associated with OS in osteosarcoma patients (HR = 3.36; 95% CI 1.02 - 11.07; P = 0.05) and in gastric cancer patients (HR = 2.17; 95% CI 1.08 - 4.38; P = 0.03). We performed the sensitivity analysis to assess the stability of the meta-analysis. A significant association was found in studies with adjustment (HR = 2.01; 95% CI 1.35 - 2.99; P= 0.0006). In conclusion, this meta-analysis suggested that high expression of HULC was significantly associated with OS of cancer.
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The present study aimed to determine the diagnostic concordance of plasma epidermal growth factor receptor (EGFR) mutation using droplet digital polymerase chain reaction (ddPCR) with tumor tissue samples and the predictive clinical significance of plasma EGFR mutation concentration. Plasma DNA samples from patients with non-small cell lung cancer (NSCLC) were analyzed for EGFR exon 21 codon 858 (L858R) mutation, deletion of exon 19 (ex19del) and exon 20 codon 790 (T790M) mutation using ddPCR. Firstly, the mutations in the plasma samples were compared with the matched tumor samples to determine the concordance. Secondly, image examination follow-ups were analyzed to assess the association between plasma EGFR mutation concentration and patients' response to EGFR-tyrosine kinase inhibitors (TKIs). A total of 51 patients with NSCLC were enrolled, including 48 newly diagnosed patients. Compared with tumor tissue samples, the sensitivity and specificity of ddPCR were 76.19% (16/21) and 96.55% (28/29) for mutant L858R, and 88.89% (8/9) and 100% (41/41) for ex19del, respectively. No patient exhibited the T790M mutation in the tumor tissue or plasma samples. Furthermore, 5 patients with the L858R mutation and 4 patients with ex19del in plasma and tumor tissue samples had been followed up with image examination for ≥3 months following EGFR-TKI treatment. The baseline mutant EGFR concentrations were positively correlated with a reduction in tumor burden (Spearman's r=0.7000, P=0.0358). When analyzed separately, ex19del concentrations (Spearman's r=1.0000, P<0.0001) were also positively correlated with the reduction, while mutant L858R concentrations were not (Spearman's r=0.7000, P=0.1881). In the present study, detection of plasma EGFR mutations using ddPCR exhibited sufficient concordance with tumor tissue sample results. Baseline plasma mutant EGFR and ex19del concentrations were significantly and positively correlated with response to EGFR-TKIs.
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Progress in the treatment options for small cell lung cancer (SCLC) remains poor. Concerns exist regarding the efficacy of bevacizumab in SCLC. The present study aimed to evaluate the efficacy of bevacizumab in extensive stage (ES)-SCLC. A meta-analysis on studies conducted and listed on the Medline, Cochrane Trials, ASCO, ESMO and ClinicalTrial databases, and Chinese databases prior to April 2015 was performed. All clinical trials in which patients with ES-SCLC were treated with bevacizumab were considered. Survival rates at specific time points were extracted from the reported survival curves. Hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS), rates for PFS, OS, overall response rate (ORR), and side-effects were synthesized using random-effects or fixed-effects model. Two randomized control trials (RCT) (176 patients) and six single-arm trials (292 patients) were identified. In RCTs, no statistically significant differences were observed in PFS [HR, 0.70; 95% confidence interval (CI), 0.41-1.19; P=0.19] or OS (HR, 1.21; 95% CI, 0.84-1.75; P=0.31). In the first-line trials, pooled 6-month and 1-year PFS rates were 57% (95% CI, 39-76%) and 10% (95% CI, 4-16%), respectively. Synthesized 1-year and 2-year OS rates were 45% (95% CI, 36-54%) and 10% (95% CI, 6-14%), respectively. Reported median PFS and OS times for pretreated patients were 2.7-4.0 months and 6.3-7.4 months, respectively. Pooled ORRs were 71% (95% CI, 59-82%) in the first-line trials and 18% (95% CI, 11-25%) in the second-line trials. The most common types of reported toxicities were chemotherapy-associated, including neutropenia, leukopenia, fatigue and thrombocytopenia. According to the RCTs, bevacizumab did not appear to improve the PFS or OS for patients with ES-SCLC, with low quality of evidence. Due to the disappointing pooled efficacy in the single-arm trials, more clinical studies on bevacizumab in SCLC may not be valuable, although the evidence was with low quality.
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OBJECTIVES: Droplet digital polymerase chain reaction (ddPCR) has shown sufficient concordance in detecting plasma epidermal growth factor receptor (EGFR) status in non-small cell lung cancer (NSCLC), compared to tumor tissues. However, the clinical significance of the quantitative plasma mutated EGFR concentration remains unknown. The purpose of this study was to explore the relationship of plasma mutated EGFR concentration with tumor burden in advanced NSCLC patients. MATERIALS AND METHODS: Using ddPCR, plasma DNA samples prior to administration of therapies from 113 consecutive NSCLC patients were analyzed for EGFR L858R substitution and deletion of exon19 (ex19del). Plasma EGFR status was compared to tumor EGFR status to determine concordance. Then, we assessed the correlation of plasma mutated EGFR concentrations with tumor burden and other tumor characteristics. RESULTS AND CONCLUSION: Compared to tumor EGFR, the concordance rate of plasma and tissue EGFR status was 86.73%. Of the 64 patients who harbored tumor EGFR mutation, plasma mutated EGFR concentrations significantly correlated with number of metastatic sites (Spearman's r=0.4954, p<0.0001), number of lesions (Spearman's r=0.4484, p=0.0002), and sum of measurable lesions' diameters (Spearman's r=0.3539, p=0.0048). Number of metastatic sites was independently associated with mutated EGFR concentration in multiple linear regression. Besides, plasma mutated EGFR concentrations were significantly higher in those with extensive tumor burden (median concentration, 386.9 vs. 13.4copies/mL; p<0.0001) and stage IV disease (median concentration, 244.2 vs. 0copies/mL; p=0.0252). In conclusion, mutated plasma EGFR concentration determined by ddPCR analysis significantly correlated with tumor burden.
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Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Receptores ErbB/genética , Neoplasias Pulmonares/diagnóstico , Mutação/genética , Carga Tumoral , Carcinoma Pulmonar de Células não Pequenas/genética , Análise Mutacional de DNA , Receptores ErbB/sangue , Feminino , Humanos , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Sensibilidade e EspecificidadeRESUMO
Traditional Chinese Medicine (TCM) therapies should be tailored according to the different syndrome types. In order to identify the relationship between the TCM Yin-cold (YC) or Yang-heat (YH) syndrome types and the EGFR gene status, we prospectively studied 310 NSCLC patients. TCM YH or YC was diagnosed by three TCM experts. TCM symptoms and signs were entered into a binary cluster analysis. The relationships between the EGFR gene status, YH or YC syndrome types, and classification by cluster analysis were analyzed using the chi-square test and multivariate logistic regression. In the 299 patients who had their EGFR gene tested, 45.24% YC (76/168) and 25.95% YH (34/131) patients had EGFR mutations (p = 0.001). Among the 292 patients entered into the cluster analysis, 132 were classified into group A, with signs and symptoms similar to YC, whereas 160 group B patients were similar to YH. In the 281 patients with EGFR tested, 45.67% group A (58/127) and 28.57% group B patients (44/154) had EGFR mutations (p = 0.003). The EGFR status was independently correlated with TCM syndrome type and classification by cluster analysis on multivariate logistic regression. NSCLC patients with YC were more likely to have EGFR gene mutations.
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Detection of circulating tumor DNA using droplet digital polymerase chain reaction (ddPCR) is a highly-sensitive, minimally invasive alternative to serial biopsies for assessment and management of cancer. We used ddPCR to assess the utility of measuring plasma concentrations of common epidermal growth factor receptor (EGFR) mutations (L858R, exon 19 deletion, and T790M) in 57 non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs). High baseline plasma EGFR mutation (pEGFRmut) concentrations were associated with shorter progression-free survival (8.43 months) than low baseline pEGFRmut (16.23 months; p = 0.0019). By contrast, there were no differences in tumor shrinkage or overall survival between groups. During EGFR-TKI treatment, pEGFRmut levels decreased to zero in 89.58% of patients. Twenty-five of the 27 patients who progressed had basal pEGFRmut, and 18 also had circulating T790M. All 20 patients with dramatic progression (according to a categorization system for EGFR-TKIs failure) had basal pEGFRmut, and 13 had T790M mutation at progression. These results support the use of ddPCR for analysis of plasma EGFR mutations for prediction of PFS and to monitor clinical responses to EGFR-TKIs in NSCLC patients.
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Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Idoso , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/genética , Intervalo Livre de Doença , Receptores ErbB/sangue , Receptores ErbB/genética , Cloridrato de Erlotinib/uso terapêutico , Feminino , Gefitinibe , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Prognóstico , Quinazolinas/uso terapêutico , Resultado do TratamentoRESUMO
Two new carboxyethyltin-functionalized polyoxometalates (POMs) were successfully obtained and confirmed with physicochemical and spectroscopic methods including X-ray crystallography. The lowest unoccupied molecular orbitals of both compounds are higher in energy than that of TiO2 , and the optical band gaps of these compounds are smaller than that of TiO2 . Grafting them onto a TiO2 film created two kinds of novel photoanode materials that showed significantly enhanced photovoltaic and photocurrent responses, as well as improved photoelectrooxidation activities for methanol relative to that shown by a single TiO2 film. Further, P2 W15 -Co-SnR produced the largest photocurrent by exploring the photoelectric activities of a series of carboxyethyltin POM derivatives. This work provides new insight into the photoelectrochemical functionalization of POM-based organic-inorganic hybrids.
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Processos Fotoquímicos , Titânio/química , Compostos de Tungstênio/química , Eletroquímica , Metanol/química , Modelos Moleculares , Conformação Molecular , Oxirredução , TemperaturaRESUMO
Objective. To evaluate the effectiveness and safety of acupuncture for cancer-related pain. Methods. A systematic review of literatures published from database inception to February 2015 was conducted in eight databases. RCTs involving acupuncture for treatment of cancer-related pain were identified. Two researchers independently performed article selection, data extraction, and quality assessment of data. Results. 1,639 participants in twenty RCTs were analyzed. All selected RCTs were associated with high risk of bias. Meta-analysis indicated that acupuncture alone did not have superior pain-relieving effects as compared with conventional drug therapy. However, as compared with the drug therapy alone, acupuncture plus drug therapy resulted in increased pain remission rate, shorter onset time of pain relief, longer pain-free duration, and better quality of life without serious adverse effects. However, GRADE analysis revealed that the quality of all outcomes about acupuncture plus drug therapy was very low. Conclusions. Acupuncture plus drug therapy is more effective than conventional drug therapy alone for cancer-related pain. However, multicenter high-quality RCTs with larger sample sizes are needed to provide stronger evidence for the effectiveness of acupuncture in cancer-related pain due to the low data quality of the studies included in the current meta-analysis.
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A Dawson sandwich-type polyoxometalate {C(NH2)3}12H4[αßßα-{(Sn(C3H4O2))2Mn2(P2W15O56)2}]·22H2O (abbreviated as SnR-Mn-P2W15), functionalized by open chain carboxyethyltin groups, was first prepared in aqueous solution under conventional reaction conditions, and then structurally characterized by physicochemical and spectroscopic methods. Single crystal X-ray diffraction analysis revealed that two Mn(2+) cations and two [Sn(CH2CH2COO)](2+) groups are located in the internal and external positions in the so-called equatorial region of SnR-Mn-P2W15, respectively. Intriguingly, two exposed carboxyl groups act as stretching-arm brackets, which provide a favorable structure for potential further functionalization. The electrocatalytic activity of SnR-Mn-P2W15 towards the reduction of hydrogen peroxide and nitrite was studied. Additionally, its acid catalysis and oxidation catalysis activities in organic synthesis were investigated.
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Compostos de Tungstênio/química , Compostos de Tungstênio/síntese química , Catálise , Técnicas de Química Sintética , Cicloexanóis/química , Cicloexanonas/química , Peróxido de Hidrogênio/química , Modelos Moleculares , Conformação Molecular , Nitritos/química , OxirreduçãoRESUMO
PURPOSE: To assess the activity and safety of postoperative adjuvant immunotherapy with transfusion of cytokine-induced killer (CIK) cells combined with chemotherapy in patients with colorectal cancer. METHODS: We retrospectively studied 96 consecutive patients with colorectal cancer who were treated with resection between January 2010 and December 2012 as well as adjuvant chemotherapy. Twenty-one of these patients accepted at least 1 cycle of CIK cell transfusion for immunotherapy (CIK group). Disease free survival (DFS), immune cells and treatment related side effects were assessed. The patients were followed up until May 2013. RESULTS: By the end of follow-up, 10 patients (10.42 %) had died. Eighteen patients (18.75 %) had withdrawn. All the patients in the CIK group are still alive, and only 1 patient had withdrawn. Patients in the CIK group had significantly longer DFS than those in the control group [HR = 0.28, 95 % CI (0.09, 0.91), p = 0.034]. The 2-year DFS rates of patients in the CIK group and the control group were 59.65 ± 24.80 % and 29.35 ± 6.39 %, respectively. The CD4(+)/CD8(+) ratios were significantly lower during the period of chemotherapy than those before chemotherapy (p = 0.0038), while the ratios were significantly higher during the period of CIK cell transfusion than those before CIK therapy (p = 0.0484). There were no immediate adverse reactions to the CIK cell transfusions. CONCLUSION: Adjuvant transfusion of CIK cells prolongs DFS in patients with colorectal cancer.
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Neoplasias Colorretais/terapia , Células Matadoras Induzidas por Citocinas/transplante , Imunoterapia Adotiva/métodos , Relação CD4-CD8 , Quimioterapia Adjuvante , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/cirurgia , Terapia Combinada , Células Matadoras Induzidas por Citocinas/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Período Pós-Operatório , Estudos Retrospectivos , Subpopulações de Linfócitos T/imunologiaRESUMO
It has become evident that some of the natural or synthetic triterpenoids are natural proteasome inhibitors that have great potential for use in cancer prevention and treatment. However, the mechanisms for the antitumor activity of triterpenoids remain to be elucidated. In the present study, we investigated the anticancer activities of a natural triterpenoid, pristimerin, and the signaling pathways affected. Pristimerin was found to possess potent cytotoxic effects, inducing apoptosis and inhibiting proliferation in U87 human glioma cells. Hoechst 33258 staining and Annexin V/PI double staining exhibited the typical nuclear features of apoptosis and increased the proportion of apoptotic Annexin V-positive cells in a dose-dependent manner, respectively. Moreover, western blotting assay revealed that this apoptotic induction was associated with activated caspase-9, caspase-3, PARP cleavage and downregulation of Bcl-xl/Bax in a concentration-dependent manner. Pristimerin also increased the generation of reactive oxygen species and induced the subsequent release of cytochrome c from the mitochondria into the cytosol. Additionally, pristimerin downregulated EGFR protein expression and inhibited downstream signaling pathways in U87 cells. Our results suggest that pristimerin may have potential as a new targeting therapeutic strategy in the treatment of EGFR-overexpressing gliomas.
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OBJECTIVE: To provide the seed cells for bone tissue engineering, to establish immortalized human bone marrow mesenchymal stem cells (MSCxj) and to investigate the ectopic osteogenesis of MSCxj. METHODS: MSCxjs of the 35th and 128th generations were maintained and harvested when the cell density reached 2 x 10(9). Then, these cells were co-cultured with heterogeneous bone scaffold in groups A (the 35th generation, n = 12) and group B (the 128th generation, n = 12); heterogeneous bone alone was used in group C (n = 12). The cell proliferation was observed by scanning electron microscopy (SEM) after 48 hours and 18 days of osteogenic induction culture. The complex was implanted subcutaneously through a 3-mm-incision at both sides of the back in 18 nude mice. Tetracycline labeling was performed before the animals were sacrificed. Tetracycline fluorescence staining, HE staining, ponceau staining, and immunohistochemistry staining for osteocalcin were performed at 4, 8, and 12 weeks after transplantation; the morphologic quantitative analysis was made. RESULTS: After 48 hours, SEM showed that MSCxjs adhered to heterogeneous bone and grew well; after 18 days, a large number of new filamentous extracellular matrix and small granules were found to cover the cells. The results of tetracycline fluorescence staining, HE staining, and ponceau staining in groups A and B showed that the osteogenesis was not obvious at 4 weeks after transplantation; osteoid matrix deposition was noted around and in the heterogeneous bone at 8 weeks; and osteogenesis was increased at 12 weeks. There was no significant difference in bone formation between groups A and B. Osteogenesis was not observed in group C. The osteocalcin expressions were positive in groups A and B. The bone ingrown percentages of groups A and B were 5.64% +/- 2.68% and 4.92% +/- 2.95% at 8 weeks, and 13.94% +/- 2.21% and 14.34% +/- 3.46% at 12 weeks, showing significant differences between 8 weeks and 12 weeks at the same group (P < 0.05) and no significant difference between groups A and B at the same time (P > 0.05). CONCLUSION: MSCxj has favorable abilities of ectopic osteogenesis and can be applied as seeded cells in bone tissue engineering.
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Células da Medula Óssea/citologia , Osso e Ossos , Células-Tronco Mesenquimais/citologia , Osteogênese , Engenharia Tecidual/métodos , Animais , Células Cultivadas , Técnicas de Cocultura , Feminino , Humanos , Camundongos , Camundongos NusRESUMO
Distributions of the optical field in a solid immersion lens recording system are calculated for higher-order radially polarized modes of the incidence. Results show that two higher-order radially polarized modes of R-TEM(11) (* )and R-TEM(21) * are useful to near-field optical recording, but further higher-order modes such as R-TEM(31) (* ), R-TEM(41) (* ), and R-TEM(51) (* ) are not useful due to the strong side-lobe intensity. Compared with R-TEM(01) (* ) beam focusing, the full width at half-maximum of the recording spot is decreased markedly and the focal depth is increased substantially by using R-TEM(11) (* )beam focusing. The effect of the beam width of the R-TEM(11) (* ) mode is also discussed.
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Cell-based tissue engineering is thought to be a new therapy for treatment of bone defects and nonunions after trauma and tumor resection. In this study, we explore the in vitro and in vivo osteogenesis of a novel biomimetic construct fabricated by using collagen I gel to suspend rabbit adipose-derived stem cells (rASCs) into a porous poly(lactic-co-glycolic)acid-beta-tricalcium phosphate (PLGA-beta-TCP) scaffold (rASCs-COL/PLGA-beta-TCP). In vitro and in vivo studies of the rASCs-COL/PLGA-beta-TCP composite (group A) were carried out compared with the single combination of rASCs and PLGA-beta-TCP (rASCs/PLGA-beta-TCP; group B), the combination of acellular collagen I gel and PLGA-beta-TCP (COL/PLGA-beta-TCP; group C), and the PLGA-beta-TCP scaffold (group D). Composites of different groups were cultured in vitro for 2 weeks in osteogenic medium and then implanted into the autologous muscular intervals for 8 weeks. After 2 weeks of in vitro culture, alkaline phosphatase activity and extracellular matrix mineralization in group A were significantly higher than in group B (p < 0.01, n = 4). In vivo osteogenesis was evaluated by radiographic and histological analyses. The calcification level was radiographically evident in group A, whereas no apparent calcification was observed in groups B, C and D (n = 4). In group A, woven bone with a trabecular structure was formed, while in group B, only osteoid tissue was observed. Meanwhile, the bone-forming area in group A was significantly higher than in group B (p < 0.01, n = 4). No bone formation was observed in groups C or D (n = 4). In conclusion, by using collagen I gel to suspend rASCs into porous PLGA-beta-TCP scaffold, osteogenic differentiation of rASCs can be improved and homogeneous bone tissue can be successfully formed in vivo.