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2.
World J Cardiol ; 15(10): 508-517, 2023 Oct 26.
Article in English | MEDLINE | ID: mdl-37900904

ABSTRACT

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is a leading cause of death worldwide. AIM: To explore factors influencing prehospital return of spontaneous circulation (P-ROSC) in patients with OHCA and develop a nomogram prediction model. METHODS: Clinical data of patients with OHCA in Shenzhen, China, from January 2012 to December 2019 were retrospectively analyzed. Least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were applied to select the optimal factors predicting P-ROSC in patients with OHCA. A nomogram prediction model was established based on these influencing factors. Discrimination and calibration were assessed using receiver operating characteristic (ROC) and calibration curves. Decision curve analysis (DCA) was used to evaluate the model's clinical utility. RESULTS: Among the included 2685 patients with OHCA, the P-ROSC incidence was 5.8%. LASSO and multivariate logistic regression analyses showed that age, bystander cardiopulmonary resuscitation (CPR), initial rhythm, CPR duration, ventilation mode, and pathogenesis were independent factors influencing P-ROSC in these patients. The area under the ROC was 0.963. The calibration plot demonstrated that the predicted P-ROSC model was concordant with the actual P-ROSC. The good clinical usability of the prediction model was confirmed using DCA. CONCLUSION: The nomogram prediction model could effectively predict the probability of P-ROSC in patients with OHCA.

3.
Microbiol Spectr ; 11(3): e0026423, 2023 06 15.
Article in English | MEDLINE | ID: mdl-37125929

ABSTRACT

Chronic pulmonary aspergillosis (CPA) is a chronic and progressive fungal disease with high morbidity and mortality. Avoiding diagnostic delay and misdiagnosis are concerns for CPA patients. However, diagnostic practice is poorly evaluated, especially in resource-constrained areas where Aspergillus antibody testing tools are lacking. This study aimed to investigate the diagnostic laboratory findings in a retrospective CPA cohort and to evaluate the performance of a novel Aspergillus IgG lateral flow assay (LFA; Era Biology, Tianjin, China). During January 2016 and December 2021, suspected CPA patients were screened at the Center for Infectious Diseases at Huashan Hospital. A total of 126 CPA patients were enrolled. Aspergillus IgG was positive in 72.1% with chronic cavitary pulmonary aspergillosis, 75.0% with chronic necrotizing pulmonary aspergillosis, 41.7% with simple aspergilloma, and 30.3% with Aspergillus nodule(s). The cavitary CPA subtypes had significantly higher levels of Aspergillus IgG. Aspergillus IgG was negative in 52 patients, who were finally diagnosed by histopathology, respiratory culture, and metagenomic next-generation sequencing (mNGS). Sputum culture was positive in 39.3% (42/107) of patients and Aspergillus fumigatus was the most common species (69.0%, 29/42). For CPA cohort versus controls, the sensitivity and specificity of the LFA were 55.6% and 92.7%, respectively. In a subgroup analysis, the LFA was highly sensitive for A. fumigatus-associated chronic cavitary pulmonary aspergillosis (CCPA; 96.2%, 26/27). Given the complexity of the disease, a combination of serological and non-serological tests should be considered to avoid misdiagnosis of CPA. The novel LFA has a satisfactory performance and allows earlier screening and diagnosis of CPA patients. IMPORTANCE There are concerns on avoiding diagnostic delay and misdiagnosis for chronic pulmonary aspergillosis due to its high morbidity and mortality. A proportion of CPA patients test negative for Aspergillus IgG. An optimal diagnostic strategy for CPA requires in-depth investigation based on real-world diagnostic practice, which has been rarely discussed. We summarized the clinical and diagnostic laboratory findings of 126 CPA patients with various CPA subtypes. Aspergillus IgG was the most sensitive test for diagnosing CPA. However, it was negative in 52 patients, who were finally diagnosed by non-serological tests, including biopsy, respiratory culture, and metagenomic next-generation sequencing. We also evaluated a novel Aspergillus IgG lateral flow assay, which showed a satisfactory performance in cavitary CPA patients and was highly specific to Aspergillus fumigatus. This study gives a full picture of the diagnostic practice for CPA patients in Chinese context and calls for early diagnosis of CPA with combined approaches.


Subject(s)
Delayed Diagnosis , Pulmonary Aspergillosis , Humans , Retrospective Studies , Pulmonary Aspergillosis/diagnosis , Aspergillus/genetics , Immunoglobulin G , Aspergillus fumigatus , Persistent Infection , Antibodies, Fungal , Chronic Disease
4.
Mycoses ; 66(4): 308-316, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36520582

ABSTRACT

BACKGROUND: Central nervous system (CNS) aspergillosis is an uncommon but fatal disease, the diagnosis of which is still difficult. OBJECTIVES: We aim to explore the diagnositic performance of noncultural methods for CNS aspergillosis. METHODS: In this retrospective study, all pathologically confirmed rhinosinusitis patients in whom cerebrospinal fluid (CSF) galactomannan (GM) test and metagenomic next-generation sequencing (mNGS) had been performed were included. We evaluated the diagnostic performances of CSF GM optical density indexes (ODI) at different cut-off values and compared performance with mNGS in patients with and without CNS aspergillosis, as well as in patients with different manifestations of CNS aspergillosis. RESULTS: Of the 21 proven and probable cases, one had positive culture result, five had positive mNGS results and 10 had a CSF GM ODI of >0.7. Sample concordance between mNGS and GM test was poor, but best diagnostic performance was achieved by combination of GM test (ODI of >0.7) and mNGS, which generated a sensitivity of 61.9% and specificity of 82.6%. Further investigation of combination diagnostic performances in different kind of CNS aspergillosis was also conducted. Lowest sensitivity (42.9%) was identified in abscess group, while increased sensitivity (60.0%) was achieved in abscess with encephalitis groups. Combination test exhibited the best performance for encephalitis patients who had only CSF abnormalities, in whom the sensitivity and specificity were 77.8% and 82.6%, respectively. CONCLUSIONS: In conclusion, combination of these two tests might be useful for diagnosis of CNS aspergillosis associated with fungal rhinosinusitis, especially in encephalitis patients.


Subject(s)
Aspergillosis , Encephalitis , Humans , Retrospective Studies , Abscess , Granulocyte-Macrophage Colony-Stimulating Factor , Aspergillosis/diagnosis , Sensitivity and Specificity , Mannans , Central Nervous System
5.
Oncol Rep ; 43(2): 461-470, 2020 02.
Article in English | MEDLINE | ID: mdl-31894342

ABSTRACT

In recent years, the important role of long non­â€‹coding RNAs (lncRNAs) in the development of liver cancer has received increasing attention. The abnormal expression level of long non­coding RNAs has been associated with the occurrence and development of liver cancer. However, the role and molecular mechanisms of lncRNAs in the development and progression of liver cancer are not fully understood. The present study aimed to clarify the function and molecular mechanism of lncRNA brain cytoplasmic 200 (BC200) in liver cancer. In the present study, it was found that BC200 expression level was higher in hepatocellular carcinoma (HCC) tissues than that in adjacent tissues. Cell function was examined by constructing BC200 knockout (KO) and BC200­overexpression in vitro models. It was found that BC200 affected the proliferation and migration of HepG2 cells. Interestingly, it was found that BC200 affected the expression of c­Myc protein but did not affect the mRNA expression level of c­MYC. BC200 KO cells exhibited a reduced protein expression level of Bax protein and an increased protein expression level of Bcl­xL. Conversely, BC200 overexpression reduced the expression of Bcl­xL protein and increased the expression of Bax protein. Importantly, it was found that BC200 affected the formation of subcutaneous tumors in nude mice. In conclusion, the present results suggested that lncRNA BC200 may play an important role in liver cancer.


Subject(s)
Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , RNA, Long Noncoding/genetics , Up-Regulation , Adult , Animals , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Cell Movement , Cell Proliferation , Female , Gene Expression Regulation, Neoplastic , Hep G2 Cells , Humans , Liver Neoplasms/genetics , Male , Mice , Middle Aged , Neoplasm Transplantation , Proto-Oncogene Proteins c-myc/genetics , Proto-Oncogene Proteins c-myc/metabolism
6.
Open Forum Infect Dis ; 5(10): ofy228, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30302354

ABSTRACT

BACKGROUND: Chronic and granulomatous invasive fungal rhinosinusitis are important causes of blindness and craniocerebral complications. However, the classification of these 2 diseases remains controversial. METHODS: We retrospectively analyzed patients with chronic and granulomatous invasive fungal rhinosinusitus in a Chinese tertiary hospital from 2009 to 2017, with a focus on classification and comparisons. RESULTS: Among 55 patients enrolled in our study, 11 (11/55, 20%) had granulomatous invasive fungal rhinosinusitis (GIFRS) and 44 (44/55, 80%) had chronic invasive fungal rhinosinusitis (CIFRS). Aspergillus fumigatus and Dematiaceous hyphomycetes were identified in 2 patients with GIFRS. Compared with granulomatous type, CIFRS was more frequently encountered in immunocompromised patients (P = .022), and the time from onset to diagnosis was much shorter (P = .001). Proptosis and orbital apex syndrome showed no significant difference between granulomatous and CIFRS in our study. The treatment options and prognosis of both diseases also showed no significant difference. CONCLUSIONS: Despite the consensus on histopathology, the classification of the chronic and granulomatous types may need further evaluation in clinical considerations.

7.
Dis Markers ; 2018: 9845123, 2018.
Article in English | MEDLINE | ID: mdl-30647803

ABSTRACT

BACKGROUND: The correlation between tumor markers (TM) and TNM stage of non-small-cell lung cancer (NSCLC) has not been widely reported. METHODS: TM levels (CEA, CA125, CA15-3, CA19-9, CA72-4, CYFRA21-1, and SCC-Ag) in 424 cases of lung adenocarcinoma (LAC), 166 cases of lung squamous cell carcinoma (LSCC), and 103 cases of benign chest disease (BCD) were analyzed before treatment. RESULTS: By Kendall's tau-b correlation analysis, CEA, CA125, CA15-3, CA19-9, CA72-4, CYFRA21-1, and SCC-Ag were correlated with T stage of LAC (r = 0.235, p < 0.05; r = 0.298, p < 0.05; r = 0.254, p < 0.05; r = 0.063, p < 0.05; r = 0.080, p < 0.05; r = 0.268, p < 0.05; and r = 0.080, p < 0.05). CEA, CA125, CA15-3, CA19-9, CA72-4, and CYFRA21-1 were correlated with N stage of LAC (r = 0.356, p < 0.05; r = 0.415, p < 0.05; r = 0.340, p < 0.05; r = 0.117, p < 0.05; r = 0.175, p < 0.05; and r = 0.351, p < 0.05). CEA, CA125, CA15-3, CA19-9, CA72-4, and CYFRA21-1 were correlated with M stage of LAC (r = 0.365, p < 0.05; r = 0.353, p < 0.05; r = 0.293, p < 0.05; r = 0.135, p < 0.05; r = 0.169, p < 0.05; and r = 0.312, p < 0.05). CA125, CYFRA21-1, and SCC-Ag were correlated with T stage of LSCC (r = 0.202, p < 0.05; r = 0.233, p < 0.05; and r = 0.099, p < 0.05). CA125 and CYFRA21-1 were correlated with N stage of LSCC (r = 0.178, p < 0.05 and r = 0.284, p < 0.05). CA125, CA15-3, and CYFRA21-1 were correlated with M stage of LSCC (r = 0.214, p < 0.05; r = 0.152, p < 0.05; and r = 0.213, p < 0.05). Combining hazard ratio, AUC, sensitivity, specificity, NPV, and PPV, it was concluded that CEA and CYFRA21-1were the most related TM of LAC. SCC-Ag and CYFRA21-1 were the most related TM of LSCC. CONCLUSIONS: CEA combined with CYFRA21-1 contributed to auxiliary diagnosis of LAC. CYFRA21-1 combined with SCC-Ag contributed to auxiliary diagnosis of LSCC. CEA, CA125, CA15-3, CA19-9, CA72-4, and CYFRA21-1 were correlated with primary tissue and metastasis of LAC. CA125 and CYFRA21-1 were correlated with primary tissue and metastasis of LSCC.


Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Non-Small-Cell Lung/diagnosis , Lung Neoplasms/diagnosis , Adult , Aged , Aged, 80 and over , Antigens, Neoplasm/metabolism , Antigens, Tumor-Associated, Carbohydrate/metabolism , CA-125 Antigen/metabolism , Carcinoembryonic Antigen/metabolism , Carcinoma, Non-Small-Cell Lung/metabolism , Female , Humans , Keratin-19/metabolism , Lung Neoplasms/metabolism , Male , Membrane Proteins/metabolism , Middle Aged , Mucin-1/metabolism , Neoplasm Staging , Sensitivity and Specificity , Young Adult
8.
Chin J Nat Med ; 15(7): 534-539, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28807227

ABSTRACT

The present study was designed to investigate the anti-sepsis effects of physcion 8-O-ß-glucopyranoside (POG) isolated from Rumex japonicas and explore its possible pharmacological mechanisms. POG was extracted from R. japonicas by bioactivity-guided isolation with the anti-sepsis agents. Survival analysis in septic mouse induced by LPS and heat-killed Escherichia coli were used to evaluate the protective effect of POG (40 mg·kg-1, i.p.) on sepsis. Cytokines including TNF-α, IL-1ß and IL-6 in RAW 264.7 cells induced by LPS (100 ng·mL-1) were determined by ELISA. In addition, the proteins expressions of TLR2 and TLR4 were determined by Western blotting assay. Our results demonstrated that POG (40 mg·kg-1, i.p.) possessed significant protective activity on the endotoxemic mice. The POG treatment (20, 40, and 80 µg·mL-1) significantly decreased the TNF-α, IL-1ß and IL-6 induced by LPS (P < 0.01) in a concentration-dependent manner. Furthermore, the TLR4 and TLR2 proteins were also down-regulated by POG at 20 (P < 0.01), 40 (P < 0.01), and 80 µg·mL-1 (P < 0.01). The present study demonstrated that the POG extracted from R. japonicas possessed significant anti-sepsis effect on endotoxemic mice, and can be developed as a novel drug for treating sepsis in the future.


Subject(s)
Anti-Inflammatory Agents/administration & dosage , Drugs, Chinese Herbal/administration & dosage , Emodin/analogs & derivatives , Glucosides/administration & dosage , Rumex/chemistry , Sepsis/drug therapy , Animals , Emodin/administration & dosage , Humans , Interleukin-1beta/genetics , Interleukin-1beta/immunology , Interleukin-6/genetics , Interleukin-6/immunology , Interleukin-8/genetics , Interleukin-8/immunology , Macrophages/drug effects , Macrophages/immunology , Male , Mice , Mice, Inbred ICR , RAW 264.7 Cells , Sepsis/genetics , Sepsis/immunology , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/immunology
9.
J Proteomics ; 77: 480-91, 2012 Dec 21.
Article in English | MEDLINE | ID: mdl-23041135

ABSTRACT

The oligodendroglioma (OG) type of glial cell tumors accounts for 2-5% of primary brain neoplasms and 4-15% of gliomas diagnosed worldwide. Allelic losses on 1p, or on 1p and 19q, correlate with chemotherapy response and good prognosis in OG patients; however, the underlying mechanisms are not yet clearly defined. Therefore, we utilized a quantitative proteomics strategy that combined 8-plex isobaric tags for relative and absolute quantitation (iTRAQ) labeling and two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC/MS/MS) to identify molecular signatures, reveal mechanisms, and develop predictive markers of OG patients with 1p loss of heterozygosity (LOH). An initial screening of four OG patients with 1p LOH and four without were identified, and 449 differentially expressed proteins were quantified, 13 of which were significantly different between the two groups. Analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway suggested that 1p LOH may affect the actin network in OG. The differential expression of four of the 13 candidates (UBA1, ubiquitin-like modifier activating enzyme 1; ATP6V1E1, ATPase, H+ transporting, lysosomal 31 kDa, V1 subunit E1; MAP2, microtubule-associated protein 2; and HMGB1, high-mobility group protein B1) was validated in 39 additional OG samples using immunohistochemistry. Decision tree modeling indicated that MAP2 expression is a powerful predictor of 1p LOH. Our results not only demonstrate the utility of iTRAQ-based high-throughput quantitative proteomic analysis in glioma research, but also provide novel markers that may help to reveal the mechanisms of 1p LOH-associated chemosensitivity, and to design diagnostic and prognostic assays and therapeutics for OG.


Subject(s)
Biomarkers, Tumor/metabolism , Brain Neoplasms/metabolism , Chromosomes, Human, Pair 1 , Loss of Heterozygosity , Neoplasm Proteins/metabolism , Nerve Tissue Proteins/metabolism , Oligodendroglioma/metabolism , Biomarkers, Tumor/genetics , Brain Neoplasms/drug therapy , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Chromosomes, Human, Pair 19 , Female , Humans , Male , Neoplasm Proteins/genetics , Nerve Tissue Proteins/genetics , Oligodendroglioma/drug therapy , Oligodendroglioma/genetics , Oligodendroglioma/pathology , Proteomics/methods
10.
Nan Fang Yi Ke Da Xue Xue Bao ; 31(6): 1086-9, 2011 Jun.
Article in Chinese | MEDLINE | ID: mdl-21690076

ABSTRACT

OBJECTIVE: To investigate the effect of intraluminal administration of ulinastatin (a protease inhibitor) in the intestine on intestinal inflammation in rats with hemorrhagic shock. METHODS: Twenty-eight Wistar rats were randomized into control group (A), intestinal saline perfusion group (B), ulinastatin intestinal perfusion group (C), and intravenous ulinastatin injection group (D) (n=7). The mean arterial blood pressure (MAP) and survival time of the rats were recorded. The changes in human polymorphonuclear cell (PMN) CD11b expression were detected by flow cytometry. The leukocyte count was recorded at different time points after the treatment, and the pathology of the intestinal mucosa was observed comparatively. RESULTS: Groups C and D showed significantly slower reduction of the MAP than groups A and B after hemorrhagic shock (P<0.05). The survival time of the rats was the longest in group C (P<0.05). CD11b expression increased gradually during hemorrhagic shock in all the groups, but the expression level was the lowest in group C (P<0.05). Hemorrhagic shock caused a reduction in leukocyte counts, which remained the highest in group C (P<0.05). Group C also showed the least intestinal pathology among the 4 groups. CONCLUSION: Intestinal perfusion of ulinastatin can lower the reduction rate of MAP, attenuate plasma activation and intestinal inflammation, and prolong the survival of rats with hemorrhagic shock. These results indicate an important role of protease in intestinal inflammation during hemorrhagic shock.


Subject(s)
Inflammation , Intestines/enzymology , Shock, Hemorrhagic/enzymology , Animals , Arterial Pressure , Disease Models, Animal , Glycoproteins/administration & dosage , Glycoproteins/pharmacology , Inflammation/enzymology , Inflammation/metabolism , Intestinal Mucosa/metabolism , Plasma/metabolism , Rats , Rats, Wistar , Shock, Hemorrhagic/blood , Shock, Hemorrhagic/metabolism , Trypsin Inhibitors/administration & dosage , Trypsin Inhibitors/pharmacology
11.
Zhonghua Bing Li Xue Za Zhi ; 39(6): 372-6, 2010 Jun.
Article in Chinese | MEDLINE | ID: mdl-21055152

ABSTRACT

OBJECTIVES: This study try to subclassify breast cancer into different prognostic subgroups according to immunohistochemical algorithm and discuss the relationship between subtypes and biological and clinical behavior and prognosis. METHODS: One hundred and twenty-eight cases of infiltrative ductal carcinoma were studied using immunohistochemical staining with an antibody panel of ER, PR, HER2 and CK5/6 and subclassified referring to previous reports, and the 9 cases of HER2 positive subtype were tested using FISH. RESULTS: The expression of ER, PR, HER2, and CK5/6 was detected in 67%, 45%, 27% and 27% cases, respectively. All cases were subclassified into five subgroups, with luminal A (55%), luminal B (20%), HER2 positive (7%), basal-like (10%) and unclassified cases (8%). Nine HER2 positive cases all showed amplification of HER2 gene. It was demonstrated that the luminal A group was associated with the best prognosis but the basal-like group worst by univariate analysis. Multivariate analysis demonstrated that both the clinical stage and immunohistochemical subtypes of tumor were related to overall survival. Menses status were different among these subtypes. CONCLUSION: According to the expression of ER, PR, HER2 and CK5/6, infiltrative ductal carcinoma could be subclassified into five subgroups with different biological features and outcome, having a role in evaluating the prognosis and guiding the clinical treatment.


Subject(s)
Breast Neoplasms/classification , Carcinoma, Ductal, Breast/classification , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Adult , Aged , Aged, 80 and over , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Carcinoma, Basal Cell/metabolism , Carcinoma, Basal Cell/pathology , Carcinoma, Ductal, Breast/metabolism , Carcinoma, Ductal, Breast/pathology , Female , Follow-Up Studies , Humans , Keratin-5/metabolism , Keratin-6/metabolism , Middle Aged , Neoplasm Staging , Prognosis , Receptors, Progesterone/metabolism , Survival Rate , Tumor Burden
12.
Nan Fang Yi Ke Da Xue Xue Bao ; 30(3): 502-5, 2010 Mar.
Article in Chinese | MEDLINE | ID: mdl-20335120

ABSTRACT

OBJECTIVE: To investigate the pharmacokinetics and pharmacodynamics of poly (lactide-co-glycolide) microspheres containing ropivacaine and dexamethasone for sciatic nerve block in mice. METHODS: A total of 165 female mice were randomly assigned into 3 groups, namely dexamethasone-loaded ropivacaine microsphere group (group A, n=55), ropivacaine microsphere group (group B, n=55) and PLGA microsphere group (group C, n=55). The mice received surgical implantation of the corresponding preparations near the sciatic nerve at the dose of 400 mg/kg. Hot plate test was used to evaluate the anesthetic effect of these microspheres at different time points after the implantation, and high-performance liquid chromatography (HPLC) was employed to determine plasma ropivacaine concentration. RESULTS: Pharmacodynamic study showed that the duration of sciatic nerve sensory block was significantly longer in group A than in group B (P<0.05). The analysis of pharmacokinetics variables demonstrated that T(1/2) in group A was prolonged as compared with that of group B. No anesthetic effect was observed in group C. CONCLUSION: Dexamethasone-loaded ropivacaine microspheres can significantly prolong the analgesic effect of ropivacaine in mice.


Subject(s)
Amides/pharmacokinetics , Dexamethasone/pharmacokinetics , Lactic Acid/chemistry , Nerve Block/methods , Polyglycolic Acid/chemistry , Sciatic Nerve , Amides/pharmacology , Anesthetics, Local/pharmacokinetics , Anesthetics, Local/pharmacology , Animals , Delayed-Action Preparations , Dexamethasone/pharmacology , Female , Mice , Microspheres , Polylactic Acid-Polyglycolic Acid Copolymer , Random Allocation , Ropivacaine
13.
Cancer Sci ; 101(1): 80-6, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19860849

ABSTRACT

Special AT-rich sequence binding protein (SATB) 1 has been proposed to act as a determinant for the acquisition of metastatic activity by controlling expression of a specific set of genes that promote metastatic activity. Here we found that SATB1 expression is upregulated in multidrug-resistant breast cancer cells that exhibit higher invasive potential than the parental cells. Apart from accelerating metastasis and inducing epithelial-mesenchymal transition, SATB1 was demonstrated to confer resistance to both P-glycoprotein-related and P-glycoprotein-non-related drugs on MCF7 cells, which was accompanied by decreasing accumulation of adriamycin in SATB1-overexpressing transfectants. SATB1 depletion could partially reverse the multidrug resistance (MDR) phenotype of MCF7/ADR in vitro and in vivo. The SATB1-induced P-glycoprotein-mediated MDR could be reversed by treatment with anti-P-glycoprotein mAb. Moreover, SATB1 plays an important role in anti-apoptotic activity in MCF7/ADR cells in response to adriamycin treatment, which suggests another mechanism contributing to SATB1-related MDR of breast cancers. These data provide new insights into the mode by which breast tumors acquire the MDR phenotype and also imply a role for SATB1 in this process.


Subject(s)
Breast Neoplasms/drug therapy , Matrix Attachment Region Binding Proteins/physiology , ATP Binding Cassette Transporter, Subfamily B, Member 1/physiology , Animals , Cell Line, Tumor , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Female , Humans , Matrix Attachment Region Binding Proteins/genetics , Mice
15.
Clin Cancer Res ; 15(8): 2657-65, 2009 Apr 15.
Article in English | MEDLINE | ID: mdl-19336515

ABSTRACT

PURPOSE: Besides its therapeutic effects, chemotherapeutic agents also enhance the malignancy of treated cancers in clinical situations. Recently, epithelial-mesenchymal transition (EMT) has attracted attention in studies of tumor progression. We aimed to test whether transient Adriamycin treatment induces EMT and apoptosis simultaneously in cancer cells, clarify why the same type of cells responds differentially (i.e., apoptosis, EMT) to Adriamycin treatment, and elucidate the role of Twist1, the master regulator of EMT, in this process. EXPERIMENTAL DESIGN: In unsynchronized MCF7 cells or cells synchronized at different phases, apoptosis, EMT, and concurrent events [multidrug resistance (MDR) and tumor invasion] after Adriamycin or/and Twist1 small interfering RNA treatment were examined in vitro and in vivo. The Adriamycin-induced Twist1 expression and the interaction of Twist1 with p53-Mdm2 were examined by immunoblotting and immunoprecipitation, respectively. RESULTS: We showed in vitro that Adriamycin induced EMT and apoptosis simultaneously in a cell cycle-dependent manner. Only the cells undergoing EMT displayed enhanced invasion and MDR. Twist1 depletion completely blocked the mesenchymal transformation, partially reversed MDR, and greatly abolished invasion induced by Adriamycin. Also, we confirmed in vivo that Twist1 RNA interference improved the efficacy of Adriamycin for breast cancers. Further, Twist1 reduction in Adriamycin-treated cells promoted p53-dependent p21 induction and disrupted the association of p53 with Mdm2. CONCLUSIONS: Our studies show the diverse responses to Adriamycin treatment in cells at different phases, suggest an unrecognized role of EMT in regulating MDR and invasion, and show the efficacy of Twist1 RNA interference in Adriamycin-based chemotherapies for breast cancer.


Subject(s)
Antibiotics, Antineoplastic/adverse effects , Breast Neoplasms/pathology , Doxorubicin/adverse effects , Drug Resistance, Multiple/drug effects , Drug Resistance, Neoplasm/drug effects , Nuclear Proteins/metabolism , Twist-Related Protein 1/metabolism , Animals , Antibiotics, Antineoplastic/pharmacology , Apoptosis/drug effects , Apoptosis/physiology , Breast Neoplasms/metabolism , Cell Line, Tumor , Cyclin-Dependent Kinase Inhibitor p21/metabolism , Doxorubicin/pharmacology , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Epithelial Cells/pathology , Humans , Kaplan-Meier Estimate , Mesoderm/drug effects , Mesoderm/metabolism , Mesoderm/pathology , Mice , Mice, Nude , Neoplasm Invasiveness , Nuclear Proteins/genetics , Proto-Oncogene Proteins c-mdm2/metabolism , RNA, Small Interfering/metabolism , Tumor Suppressor Protein p53/metabolism , Twist-Related Protein 1/genetics
16.
Nan Fang Yi Ke Da Xue Xue Bao ; 27(12): 1892-5, 2007 Dec.
Article in Chinese | MEDLINE | ID: mdl-18159013

ABSTRACT

OBJECTIVE: To investigate the effect of early goal-directed therapy (EGDT) on the incidence, severity and mortality of multiple organ dysfunction syndrome (MODS). METHODS: A prospective, randomized controlled trial was performed involving 273 patients in the early stage of shock at risk of potential MODS development. The patients were randomly divided into EGDT group (including 139 patients managed with EGDT) and control group (including 134 patients with conventional empirical therapy). The scores of APACHE II, blood lactate concentration (Lactate(0)) and SOFA scores (SOFA(0)) of the two groups were recorded on admission, and the lactate concentration on the second and fourth day of hospitalization (Lactate(2) and Lactate(4)), and the highest SOFA scores (SOFAT) after admission were also recorded. The discrepancy between the two SOFA scores (SOFA(S)), number of the dysfunctional organ, and the mortality in ICU of the two groups were calculated at the end of the study. RESULTS: The incidence of MODS in the EGDT group was significantly lower than that in control group (P=0.002). The Lactate(2), Lactate(4), SOFA(T), SOFA(S), and the number of dysfunctional organs in EGDT group were also significantly lower (P=0.045, 0.016, 0.009, 0.010, 0.002). EGDT was associated with a significantly lower total mortality rate of MODS than the conventional therapy (P=0.007), and also with a significantly lower mortality rate of MODS after controlling for severe sepsis (P=0.047 and 0.044). CONCLUSION: EGDT can decrease the incidence and severity of MODS, and can effectively decrease the mortality of MODS irrespective of the presence of severe sepsis.


Subject(s)
Multiple Organ Failure/therapy , APACHE , Adult , Aged , Female , Humans , Incidence , Lactic Acid/blood , Male , Middle Aged , Multiple Organ Failure/mortality , Prospective Studies , Severity of Illness Index , Treatment Outcome
17.
Nan Fang Yi Ke Da Xue Xue Bao ; 26(6): 802-4, 817, 2006 Jun.
Article in Chinese | MEDLINE | ID: mdl-16793604

ABSTRACT

OBJECTIVE: To evaluate the effects of ketamine on perioperative serum cytokine levels in patients undergoing orthotopic liver transplantation (OLT). METHODS: Twenty patients undergoing OLT were randomly divided into ketamine group (n=10) and control group (n=10). Patients in ketamine group were given intravenous bolus injection of ketamine at 0.25 mg/kg followed by ketamine infusion at 0.5 mg.kg(-1).h(-1) until the end of operation except in the anhepatic phase, whereas the control group received saline of the same amount. Arterial blood samples were obtained at the start of surgery (T(1)), 5 min before the anhepatic phase (T(2)), 5 min before recirculation (T(3)), 15 and 60 min after recirculation (T(4), T(5)), and 0, 4 and 24 h after operation (T(6), T(7), T(8)). Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and IL-10 were measured by ELISA. RESULTS: Serum TNF-alpha, IL-6 and IL-10 levels increased significantly during anhepatic phase as compared with the baseline level (T(1)) (P<0.05), and the changes were especially obvious in IL-6 and IL-10. The levels of the cytokines kept rising after recirculation and reached the peak level at T(5)(P<0.05), followed then by rapid decline and still maintaining higher levels than the preoperative ones 24 h after operation. The levels of TNF-alpha in ketamine group between T(2) and T(7) were significantly lower than that in the control group, and the IL-6 level between T(2) and T(5) were also significantly lower in ketamine group. Serum IL-10 level did not show any significant difference between the two groups. CONCLUSION: Ischemia and reperfusion injury of the liver and surgical stress induce pro- and anti-inflammatory cytokine responses during liver transplantation, in which event IL-6 and IL-10 are more sensitive than TNF-alpha. Ketamine can inhibit the production of TNF-alpha and IL-6 but not IL-10.


Subject(s)
Interleukin-6/blood , Ketamine/administration & dosage , Liver Transplantation/methods , Tumor Necrosis Factor-alpha/blood , Anesthetics, Dissociative/administration & dosage , Female , Humans , Liver Cirrhosis/blood , Liver Cirrhosis/surgery , Liver Neoplasms/blood , Liver Neoplasms/surgery , Male , Perioperative Care
18.
Nan Fang Yi Ke Da Xue Xue Bao ; 26(1): 128-9, 2006 Jan.
Article in Chinese | MEDLINE | ID: mdl-16495194

ABSTRACT

OBJECTIVE: To evaluate the preventive and therapeutic effect of thymosin alpha(1) on lung infections in critical patients with tracheotomy. METHODS: Forty-two patients were randomly divided into treatment group and control group to receive daily subcutaneous thymosin injection at 11.6 mg and saline of 2 ml for 7 days, respectively. RESULTS: Compared with the control group, the infection rate, white blood cell count, C-reactive protein, tumor necrosis factor-alpha and interleukiu-6 were significantly lower in the treatment group. CONCLUSION: Thymosin alpha(1) can be effective for prevention and treatment of lung infections in critical patients with tracheotomy and may improve the patients' immunity and prognosis.


Subject(s)
Adjuvants, Immunologic/therapeutic use , Brain Injuries/drug therapy , Pneumonia/prevention & control , Thymosin/analogs & derivatives , Tracheotomy/adverse effects , Adolescent , Adult , Aged , Brain Injuries/surgery , Cerebral Infarction/drug therapy , Critical Illness , Female , Humans , Intensive Care Units , Male , Middle Aged , Thymalfasin , Thymosin/therapeutic use
19.
Di Yi Jun Yi Da Xue Xue Bao ; 24(6): 665-9, 2004 Jun.
Article in Chinese | MEDLINE | ID: mdl-15201085

ABSTRACT

OBJECTIVE: To study the mechanism of respiratory distress syndrome (RDS) induced by immersion in seawater to provide experimental evidence for its treatment. METHODS: Twelve normal hybrid dogs were randomly assigned into control group (n=4) and SDS model group (n=8). The changes in blood dynamics, blood gas analysis and histological changes in the lung tissues were compared between the 2 groups. The concentration of lactic dehydrogenase (LDH-L) and alkaline phosphatase (ALP) in the bronchoalveolar fluid and blood of the dogs in the model group were tested. RESULTS: The blood dynamics, blood gas analysis and histology of the dogs in the model group were significantly different from those in the control group, and LDH-L and ALP levels increased significantly in the bronchoalveolar fluid of the model group. CONCLUSION: Seawater aspiration into the lungs may lead to RDS, and the canine models used in this study may help explore the mechanism and management of RDS induced by immersion in seawater.


Subject(s)
Disease Models, Animal , Respiratory Distress Syndrome/etiology , Alkaline Phosphatase/blood , Animals , Blood Pressure , Dogs , Female , Immersion , L-Lactate Dehydrogenase/blood , Lung/pathology , Male , Respiratory Distress Syndrome/pathology , Seawater
20.
Zhonghua Yi Xue Za Zhi ; 84(24): 2070-2, 2004 Dec 17.
Article in Chinese | MEDLINE | ID: mdl-15730618

ABSTRACT

OBJECTIVE: To observe the effect of injecting activated carbon ultramicroparticles around the gastric tumor before or during operation on staining lymph nodes and guiding the lymphadenectomy of gastric cancer. METHODS: Forty-three cases of gastric cancer received activated carbon (AC) ultramicroparticles around the tumor by submucosal endoscopic injection 1 approximately 6 days before the operation and/or intraoperative subserosal injection (AC group), whereas 82 cases of gastric cancer without the injection were used as control group. The number of dissected lymph nodes, number of black-stained lymph nodes and its relation to the injection time, metastasis of lymph nodes, and the side effect of the procedure were analyzed. RESULTS: The average numbers of resected lymph nodes were 34 +/- 13 in the AC group, significantly higher than that in the control group (16 +/- 9, P < 0.05). The dissected N(2) lymph nodes in the AC group was 25 +/- 9, significantly higher than that in the control group (8 +/- 4, P < 0.05). The total ratio of black-stained lymph node was 60.3% in general, 71.3% for the N1 lymph nodes and 56.3% for the N(2) lymph nodes in the AC group. Satisfactory effect of black staining of lymph nodes could be seen 2 days after local gastric tissue injection of activated carbon ultramicroparticles. The metastasis rate was 67.4% in the AC group, not significantly different from that in the control group (63.4%, P > 0.05). In the patients of AC group the metastasis rate of black-stained lymph node was 26.8%, significantly higher than that of the unstained lymph nodes (3.3%) and higher than that of the control group (18.4%). No serious side effect happened after the activated carbon ultramicroparticles injection in local gastric tissue. CONCLUSION: Local injection of activated carbon ultramicroparticles around the tumor is an effective, easy and safe procedure to guide gastric cancer lymphadenectomy.


Subject(s)
Charcoal , Coloring Agents , Lymph Node Excision/methods , Lymph Nodes/pathology , Stomach Neoplasms/pathology , Adult , Aged , Female , Gastroscopy/methods , Humans , Injections , Lymphatic Metastasis , Male , Middle Aged , Particle Size , Staining and Labeling , Stomach Neoplasms/surgery
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